Brain Microdialysate Monoamines in Relation to Circadian Rhythms, Sleep, and Sleep Deprivation – a Systematic Review, Network Meta-analysis, and New Primary Data

Julia M. L. Menon; Christ Nolten; E. J. Marijke Achterberg; Ruud N. J. M. A. Joosten; Maurice Dematteis; Matthijs G. P. Feenstra; W. H. (Pim) Drinkenburg; Cathalijn H. C. Leenaars

doi:10.5334/jcr.174

Figures & Tables

Table 1

Circadian rhythms in dopamine levels.

Reference_ID	Animals	L/D Cycle	Duration	Brain Region	Dopamine Levels
Dugovic et al (2009) [54]	Rats	6h–18h	6h	Prefrontal Cortex	Higher during DP, lower during DP
Barbier et al (2007) [55]	Rats	6h–18h	20h	Prefrontal Cortex	Fairly stable
Nakayama et al (1993) [56]	Rats	8h–20h	24h	Medial Prefrontal Cortex	Higher during DP, lower during LP No effect of extra 12h DP
Robinson et al (1991) [57]	Sheep	Natural cycle	20h	Preoptic Area	Stable during DP, higher during LP
Alfinito et al (2009) [58]	Rats	12:12	12h30	Preoptic Area	Stable
Smith et al (1992) [46]	Rats	7h–19h	18h	Striatum	Higher during DP, lower during LP
Castaneda et al (2004) A1 [59]	Rats	20h–8h	30h	Striatum	Lower during DP, higher during LP
Castaneda et al (2004) B1 [59]	Rats	6h DP–24h LP	30h	Striatum	Higher at DP onset, then decrease and reach its lowest during LP
Hood et al (2010) [60]	Rats	8h–20h	24h	Striatum	Higher during DP, lower during LP
Sano et al (1992) A [47]	Rats, young animals	6h–18h	24h	Striatum	Higher during DP, lower during LP
Sano et al (1992) B [47]	Rats, old animals	6h–18h	24h	Striatum	Same pattern but levels are lower
Sano et al (1992) C [47]	Rats, enriched milieu	6h–18h	24h	Striatum	Stable
Sano et al (1992) D [47]	Rats, isolated	6h–18h	24h	Striatum	Stable
Decker et al (2005) [53]	Rats	7h–19h	48h	Striatum	A few spikes but mean is stable between DP and LP
De Marquez-Pardo et al (2000) [52]	Rats	8h–20h	24h	Neostriatum	Higher during DP, lower during LP
Ferris et al (2014) A [48]	Rats	ZT0–ZT12	36h	Caudate Putamen	Higher during DP, lower during LP
Ferris et al (2014) B [48]	Mice	ZT0–ZT12	38h	Caudate Putamen	Peak at DP onset, higher during DP, lower during LP
Ferris et al (2014) C [48]	Mice (DAT KO)	ZT0–ZT12	38h	Caudate Putamen	Stable
Paulson et al (1994) 1 [61]	Rats	6h–20h	20h	Caudate Nucleus	Higher during DP (double the NAC levels), lower during LP
Paulson et al (1996) 1 [62]	Rats	6h–20h	18h20	Caudate Nucleus	Higher during DP, lower during LP
Murillo-Rodriguez et al (2013) [63]	Rats	7h–19h	6h	Nucleus Accumbens	Stable
Paulson et al (1994) 2 [61]	Rats	6h–20h	20h	Nucleus Accumbens	Stable
Paulson et al (1996) 2 [62]	Rats	6h–20h	18h20	Nucleus Accumbens	Higher during DP, lower during LP
Castaneda et al (2004) A2 [59]	Rats	20h–8h	30h	Nucleus Accumbens	Lower during DP, higher during LP
Castaneda et al (2004) B2 [59]	Rats	6h DP–24h LP	30h	Nucleus Accumbens	Higher during DP, lower during LP
Verhagen et al (2009) [64]	Rats	2h–14h	36h	Lateral to Nucleus Accumbens Shell	Higher during DP, lower during LP
Fetissov et al (2000) 1 [65]	Rats	6h–18h	24h	Lateral Hypothalamus	Peak at DP onset, then start to decrease after 2h. Stay stable during LP
Fetissov et al (2000) 2 [65]	Rats	6h–18h	24h	Ventromedial Hypothalamus	Gradually decrease
Izumo et al (2012) [66]	Rats	7h–19h	15h	Central Nucleus of the Amygdala	Higher during DP, lower during LP (wide error bars)

[i] Each row represents one study (i.e. an experimental group within a publication) and a qualitative description of the results. Fluctuations are described as “higher” and “lower” disregarding actual magnitude of changes. Rows are sorted by brain region. Lower case letters indicate separate publications from the same authors in the same year; upper cases letters represent separate groups within publications; numbers represent separate brain regions within animals.

Abbreviations: L/D cycle: Light-Dark Cycle; LP: Light Phase; DP: Dark Phase; DAT KO: Dopamine Transporter Knock Out; ZT: Zeitgeber.

Table 2

Circadian rhythms in DOPAC levels.

Reference_ID	Animals	L/D Cycle	Duration	Brain Region	DOPAC Levels
Ferris et al (2014) A [48]	Rats	ZT0–ZT12	36h	Caudate Putamen	Higher during DP, lower during LP
Paulson et al (1994) [61]	Rats	6h–20h	20h	Caudate Nucleus	Higher during DP, lower/stable during LP
Paulson et al (1996) [62]	Rats	6h–20h	18h20	Caudate Nucleus	Higher during DP, lower during LP
Castaneda et al (2004) A1 [59]	Rats	20h–8h	30h	Striatum	Higher during DP, lower during LP
Castaneda et al (2004) B1 [59]	Rats	6h DP–24h LP	30h	Striatum	Higher during DP, lower during LP
Hucke et al (1998) A [51]	Rats, nulliparous	6h–18h	8h	Striatum	Higher during DP, stable during LP
Hucke et al (1998) B [51]	Rats, primiparous	6h–18h	8h	Striatum	Higher during DP, stable during LP
Sano et al (1992) A [47]	Rats, young animals	6h–18h	24h	Striatum	Higher during DP, lower during LP. Highest values mid DP, lowest values mid LP
Sano et al (1992) B [47]	Rats, old animals	6h–18h	24h	Striatum	Smaller variation and level of DOPAC than young group
Sano et al (1992) C [47]	Rats, isolated	6h–18h	24h	Striatum	Stable
Sano et al (1992) D [47]	Rats, enriched environment	6h–18h	24h	Striatum	Higher levels than isolated, higher during DP, lower during LP
Smith et al (1992) [46]	Rats	7h–19h	18h	Striatum	Highest during LP, decrease gradually during the entire duration, reach lowest during DP
De Marquez-Prado et al (2000) [52]	Rats	8h–20h	24h	Neostriatum	Decrease during the entire duration (start at DP)
Castaneda et al (2004) A2 [59]	Rats	20h–8h	30h	Nucleus Accumbens	Higher during DP, lower during LP
Castaneda et al (2004) B2 [59]	Rats	6h DP–24h LP	30h	Nucleus Accumbens	Higher during DP, lower during LP.
Paulson et al (1994) [61]	Rats	6h–20h	20h	Nucleus Accumbens	Increase during LP to be the highest at DP onset. Stay stable during DP, lower during LP
Paulson et al (1996) [62]	Rats	6h–20h	18h20	Nucleus Accumbens	Higher during DP, lower during LP
Verhagen et al (2009) [64]	Rats	2h–14h	36h	Lateral to Nucleus Accumbens Shell	Higher during DP, highest at the end of DP Lowest level mid-LP. High range of fluctuation.
Nakayama et al (1993) [56]	Rats	8h–20h	24h	Medial Prefrontal Cortex	Peak at DP onset and about 3/4 DP, decrease strongly between the 2 peaks. Decrease during LP
Luo et al (2014) [67]	Rats	?	24h	SCN	Higher during DP

[i] Each row represents one study (i.e. an experimental group within a publication) and a qualitative description of the results. Fluctuations are described as “higher” and “lower” disregarding actual magnitudes of changes. Rows are sorted by brain region. Lower case letters indicate separate publications from the same authors in the same year; upper cases letters represent separate groups within publications; numbers represent separate brain regions within animals.

Abbreviations: DOPAC: 3,4-Dihydroxyphenylacetic acid; L/D Cycle: Light-Dark Cycle; LP: Light Phase; DP: Dark Phase; SCN: Suprachiasmatic Nucleus; ZT: Zeitgeber.

Table 3

Circadian rhythms in serotonin levels.

Serotonin-Circadian Rhythms
Reference_ID	Animals	L/D Cycle	Duration	Brain Region	Serotonin Levels
Huang et al (2008) [68]	Rats	6h–18h	72h	Pineal Gland	Peak at DP onset, then decrease at its lowest, before increasing again before LP. Stable during LP.
Sun et al (2002) [69]	Rats	11h–1h	312h	Pineal Gland	Increase strongly at DP onset, then decrease gradually, increase at the end. Stable during LP.
Sun et al (2003) [70]	Rats	11h–1h	132h	Pineal Gland	Peak at DP onset, gradual decrease during the rest of DP. Increase during LP.
Azekawa et al (1991) [71]	Rats	7h–19h	24h	Pineal Gland	Peak after DP onset followed by strong decrease until mid DP. Then increase until LP onset. Lower during LP
Liu et al (2005) [72]	Rats	11h–23h	72h	Pineal Gland	Peak 1h after DP onset, and 3h before LP. Nadir is seen at LP beginning, followed by a gradual increase until DP onset.
Liu et al (2006) A [73]	Rats (LEW)	6h–18h	120h	Pineal Gland	Higher after DP onset, followed by a sharp decrease until the end of DP. Levels return to baseline level and stay stable during LP
Liu et al (2006) B [73]	Rats (SD)	6h–18h	24h	Pineal Gland	Higher after DP onset but shifted compared to LEW followed by a strong decrease until the end of DP. Return to baseline level and stay stable during LP
Liu et al (2006) C [73]	Rats (Wistar TG)	6h–18h	24h	Pineal Gland	Higher at about 1/3^rd of DP, followed by a sharp decrease until the end of DP. Levels return to baseline level and stay stable during LP
Liu et al (2006) D [73]	Rats (PVG)	6h–18h	24h	Pineal Gland	Higher 1h after DP onset, followed by a decrease until the end of DP. Levels return to baseline level and stay stable during LP
Liu et al (2006) E [73]	Rats (LEW)	6h–18h	24h	Pineal Gland	Higher 3h–4h after DP onset, followed by decrease until the end of DP. Levels return to baseline level and stay stable during LP
Liu et al (2006) F [73]	Hamsters	6h–18h	24h	Pineal Gland	Peak at DP onset followed by an increase and fluctuations (less marked than in rats)
Garabette et al (2000) [74]	Rats	7h–19h	24h	Adjacent to SCN	Lower during DP. Higher during LP
Grossman et al (2000) A [75]	Hamsters	5h–19h	11h	Lateral Margin of SCN	Higher after DP onset. Stable during LP
Dudley et al (1998) A [76]	Hamsters	7h–22h	24h	Lateral Margin of the SCN	Peak at DP onset followed by gradual decrease. Stay stable during LP
Dudley et al (1998) B [76]	Hamsters	7h–22h	48h	Lateral Margin of the SCN	Peak 2h after DP onset, followed by gradual decrease. Stay stable during LP
Barassin et al (2002) [77]	Rats	12:12	17h	SCN or in Between SCN Nuclei	Peak at DP onset followed by decrease. Lower during LP
Knoch et al (2004) [78]	Hamsters	12:12	24h	SCN	Peak 2h after DP onset, followed by decrease. Lower during LP
Oshima et al (2003) [79]	Mice	6h–18h	24h	Hippocampus	Higher during DP, peak at onset and mid DP. Decrease during LP (but one peak mid LP)
Lopez-Rodriguez et al (2003) a [80]	Rats	1h–13h	24h	Posterior Hippocampus	Small peak at LP onset, yet fairly stable
Linthorst et al (1994) [81]	Rats	7h30–19h30	11h	Hippocampus	Peak at DP onset. Fairly stable during LP
Yang et al (2013) A [49]*	Mice (SERT +/+)	4h–16h	20h	Ventral Hippocampus and Ventral Striatum	Peak 3h after DP onset followed by a decrease. LP and rest of DP stable
Yang et al (2013) B [49]*	Mice (SERT +/–)	4h–16h	20h	Ventral Hippocampus and Ventral Striatum	Smaller peak 3h after DP onset followed by a sudden sharp decrease. LP and rest of DP stable. Or peak at 3h + peak 3h before LP onset. Or overall fluctuation
Yang et al (2013) C [49]*	Mice (SERT –/–)	4h–16h	20h	Ventral Hippocampus and Ventral Striatum	Gradual decrease during both DP and LP
Kalen et al (1989) [82]	Rats	12:12	24h	Caudal Hippocampus	Higher during DP, lower during LP
Penalva et al (2002) A [83]	Mice (CHR-R1 +/+)	6h–18h	18h	Dorsal Hippocampus	Higher during DP, lower during LP
Penalva et al (2002) B [83]	Mice (CHR-R1 +/–)	6h–18h	18h	Dorsal Hippocampus	Higher during DP, lower during LP
Penalva et al (2002) C [83]	Mice (CHR-R1 –/–)	6h–18h	18h	Dorsal Hippocampus	Higher during DP, lower during LP
Takahashi et al (1998) [84]	Rats	7h–17h	24h	Striatum	Higher during DP, stable during LP
Verhagen et al (2009) [64]	Rats	2h–14h	36h	Lateral to Nucleus Accumbens Shell	Higher during DP, lower during LP. Start increase 1h before DP onset, and reach its highest 5h after DP onset. Then decrease and reach nadir during mid-LP.
Izumo et al (2012) [66]	Rats	7h–19h	15h	Central Nucleus of the Amygdala	Peak at DP onset and mid DP followed each time by gradual decrease. Stable during LP
Smriga et al (2002) [85]	Rats	7h–19h	25h	Central Nucleus of the Amygdala	Peak at DP onset followed by gradual decrease. 1h before LP, increase to baseline level. Stable during LP
Dugovic et al (2009) [54]	Rats	6h–18h	6h	Prefrontal Cortex	Higher during DP, stable during LP
Barbier et al (2007) [55]	Rats	6h–18h	20h	Prefrontal Cortex	Stable
Jitsuki et al (2009) A [50]	Rats, male	5h–19h	24h	Medial Prefrontal Cortex	Fairly stable
Jitsuki et al (2009) B [50]	Rats, diestrous	5h–19h	24h	Medial Prefrontal Cortex	Higher during DP, lower during LP
Jitsuki et al (2009) C [50]	Rats, proestrous	5h–19h	24h	Medial Prefrontal Cortex	Higher during DP, lower during LP
Grossman et al (2004) [86]	Hamsters	14:10	24h	Margin of Thalamic Intergeniculate Leaflet	Higher 1h after DP onset, higher during DP Lower during LP, nadir mid LP
Sayer et al (1999) [87]	Rats	6h–18h	?	Anterior Hypothalamus	Stable during DP, slightly higher during LP
Fetissov et al (2000) 1 [65]	Rats	6h–18h	24h	Lateral hypothalamus	Stable apart from one peak during LP
Fetissov et al (2000) 2 [65]	Rats	6h–18h	24h	Ventromedial Hypothalamus	Peak 1h–2h after DP onset, followed by a return to baseline. Stable during rest of DP and LP

[i] Each row represents one study (i.e. an experimental group within a publication) and a qualitative description of the results. Fluctuations are described as “higher” and “lower” disregarding actual magnitudes of changes. Rows are sorted by brain region. Lower case letters indicate separate publications from the same authors in the same year; upper cases letters represent separate groups within publications; numbers represent separate brain regions within animals. * These studies provided average monoamine concentrations pooled for several brain regions.

Abbreviations: L/D cycle: Light-Dark Cycle; LP: Light Phase; DP: Dark Phase; LEW: Lewis; SD: Sprague-Dawley; TG: Transgenic; SERT: Serotonin Transporter; SCN: Suprachiasmatic Nucleus.

Table 4

Circadian rhythms in 5–HIAA levels.

Reference_ID	Animals	L/D Cycle	Duration	Brain Region	5–HIAA Levels
Glass et al (1993) a [88]	Hamsters	8h–22h	24h	Lateral margin of SCN	Peak at DP onset followed by a gradual decrease. Stable during LP, lower than DP
Luo et al (1999) A [89]	Hamsters, glucose intolerant	8h30–22h30 9h–23h	24h	Top of SCN	Increase during DP (peak 4h after DP onset), decreases during LP
Luo et al (1999) B [89]	Hamsters, glucose tolerant	8h30–22h30 9h–23h	24h	Top of SCN	Small peak during DP. Rather stable during LP
Barassin et al (2002) [77]	Rats	12:12	17h	SCN or in Between SCN Nuclei	Peak 4–6h after DP onset followed by decrease
Glass et al (1993) b [90]	Hamsters	7h–21h	24h	SCN	Peak 2h after DP, increase during DP, decrease during LP
Glass et al (1992) A [91]	Hamsters	8h–0h	24h	SCN	Peak 2h after DP onset, return to baseline at LP onset. Stable during LP except a decrease at 19h
Glass et al (1992) B [91]	Hamsters	8h–0h	24h	Lateral Margin of the SCN	Peak 2h after DP onset, return to baseline at LP onset. Stable during LP except a decrease at 19h
Luo et al (2000) [92]	Hamsters	0h–14h	24h	SCN	Peak at DP onset and nadir 4h DP onset. Stable during the rest of sampling time.
Glass et al (1993) c [45]	Hamsters	8h–0h	24h	SCN	Peak at DP onset, increases during DP, decreases during LP
Castaneda et al (2004) A1 [59]	Rats	20h–8h	30h	Striatum	Slight increase during DP, slight decrease during LP
Castaneda et al (2004) B1 [59]	Rats	6h DP–24h LP	30h	Striatum	Lower during DP, higher during LP
Sano et al (1992) A [47]	Rats, young animals	6h–18h	24h	Striatum	Nadir at DP onset, then increase gradually until the end of DP. Start of LP decrease gradually.
Sano et al (1992) B [47]	Rats, old animals	6h–18h	24h	Striatum	Stable
Sano et al (1992) C [47]	Rats, enriched media	6h–18h	24h	Striatum	Stable
Sano et al (1992) D [47]	Rats, isolated	6h–18h	24h	Striatum	Stable
Smith et al (1992) [46]	Rats	7h–19h	18h	Striatum	Stable
Nakayama et al (2002) [93]	Rats	8h–20h	24h	Striatum	Higher during DP, lower during LP
Takahashi et al (1998) [84]	Rats	7h–19h	24h	Striatum	Higher during DP, lower during LP
Castaneda et al (2004) A2 [59]	Rats	20h–8h	30h	Nucleus Accumbens	Higher during DP, lower during LP
Castaneda et al (2004) B2 [59]	Rats	6h DP–24h LP	30h	Nucleus Accumbens	Inconsistent during DP (fluctuation up and down), lower during LP
Paulson et al (1994) 2 [61]	Rats	6h–20h	20h	Nucleus Accumbens	Higher during DP, lower during LP
Paulson et al (1996) [62]	Rats	6h–20h	18h20	Nucleus Accumbens	Slightly higher during DP, lower during LP
Verhagen et al (2009) [64]	Rats	2h–14h	36h	Lateral to Nucleus Accumbens Shell	Higher during DP (peak around the end of DP), lower during LP
Paulson et al (1994) 1 [61]	Rats	6h–20h	20h	Caudate Nucleus	Higher during DP, lower during LP
Paulson et al (1996) [62]	Rats	6h–20h	18h20	Dorsolateral Caudate Nucleus	Higher during DP, lower during LP
Oshima et al (2003) [79]	Mice	6h–18h	24h	Hippocampus	Higher during DP, lower during LP
Nakayama et al (2002) [93]	Rats	8h–20h	24h	Hippocampus	Stable
Linthorst et al (1994) [81]	Rats	7h30–19h30	11h	Hippocampus	Fairly stable, higher at DP onset (slightly)
Kalen et al (1989) [82]	Rats	12:12	24h	Caudal Hippocampus	Stable, apart from a peak at the end of DP
Penalva et al (2002) A [83]	Mice, (CHR–R1 +/+)	6h–18h	18h	Dorsal Hippocampus	Higher during DP, lower during LP
Penalva et al (2002) B [83]	Mice, (CHR–R1 +/–)	6h–18h	18h	Dorsal Hippocampus	Higher during DP, lower during LP
Penalva et al (2002) C [83]	Mice, (CHR–R1 –/–)	6h–18h	18h	Dorsal Hippocampus	Higher during DP, lower during LP (higher levels than other mice)
Glass et al (1992) C [91]	Hamsters	8h–0h	24h	Preoptic Area	Peak at DP onset followed by gradual decrease. Stable during LP
Ezrokhi et al (2014) A [94]	Rats (CTL)	5h–19h	24h	Ventromedial Hypothalamus	Gradual decrease (start at LP)
Ezrokhi et al (2014) B [94]	Rats (SHR), treated with vehicle	5h–19h	24h	Ventromedial Hypothalamus	Higher during DP, lower during LP
Luo et al (1998) A [95]	Hamsters, glucose tolerant	8h30–22h30	25h	Ventromedial Hypothalamus	Lower level than intolerant group. Higher during DP with a peak at the end. Lower during LP
Luo et al (1998) B [95]	Hamsters, glucose intolerant	8h30–22h30	25h	Ventromedial Hypothalamus	Higher level and more fluctuations than tolerant group. Levels increases during DP with a peak at the end. Lower levels during LP
Luo et al (1998) C [95]	Hamsters (CTL)	8h30–22h30	25h	Ventromedial Hypothalamus	Fairly stable, higher during DP (slightly)
Stanley et al (1989) a [96]	Rats	9h–21h	24h	Paraventricular Nucleus	Peak 1h after DP onset followed by sudden decrease. Lower during LP
Glass et al (1992) D [91]	Hamsters	8h–0h	24h	Posterior Hypothalamus	Peak at DP onset followed by gradual decrease Stable during LP
Gonzales-Pina et al (2003) [97]	Rats	12:12	24h	Dorsal Raphe	Higher during DP, lower during LP
Azekawa et al (1991) [71]	Rats	7h–19h	24h	Pineal gland	Peak at DP onset followed by strong decrease and then a gradual increase until the end of DP. Lower levels during LP
Nakayama et al (1993) [56]	Rats	8h–20h	24h	Medial Prefrontal Cortex	Higher during DP, lower during LP
Nakayama et al (2002) [93]	Rats	8h–20h	24h	Medial Prefrontal Cortex	Higher during DP, lower during LP

[i] Each row represents one study (i.e. an experimental group within a publication) and a qualitative description of the results. Fluctuations are described as “higher” and “lower” disregarding actual magnitudes of changes. Rows are sorted by brain region. Lower case letters indicate separate publications from the same authors in the same year; upper cases letters represent separate groups within publications; numbers represent separate brain regions within animals.

Abbreviations: 5-HIAA: 5-hydroxyindoleacetic acid; L/D Cycle: Light-Dark Cycle; LP: Light Phase; DP: Dark Phase; SCN: Suprachiasmatic Nucleus; CTL: Control, SHR: Spontaneously Hypertensive Rats; CHR–R1: Corticotropin-Releasing Hormone Receptor 1.

Table 5

Circadian rhythms in noradrenaline levels.

Noradrenaline-Circadian Rhythms
Reference_ID	Animals	L/D Cycle	Duration	Brain Region	Noradrenaline Levels
Barbier et al (2007) [55]	Rats	6h–18h	20h	Prefrontal Cortex	Higher during DP, stable during LP
Dugovic et al (2009) [54]	Rats	6h–18h	6h	Prefrontal Cortex	Higher during DP, stable during LP
Robinson et al (1991) [57]	Sheep	natural	20h	Preoptic Area	Decrease gradually
Alfinito et al (2009) [58]	Rats	12:12	12h30	Preoptic Area	Higher during DP, stable during LP
Mitome et al (1994) a [37]	Rats	6h–18h	52h	Paraventricular Nucleus	Higher during DP, lower during LP
Stanley et al (1989) b [98]	Rats	9h–21h	48h	Paraventricular Nucleus	Peak 1h after DP onset, followed by sudden decrease, until a second smaller peak at 3h before LP. Lower levels during LP
Mitome et al (1994) b [99]	Rats	6h–18h	54h	Paraventricular Nucleus	Higher during DP, lower during LP
Morien et al (1995) A [100]*	Rats	7h–19h	24h	Paraventricular Nucleus	Peak 1h and 8h after DP onset. Higher during DP, lower during LP
Smriga et al (2000) b [101]	Rats	7h–19h	24h	Lateral Hypothalamus	Gradual increase from baseline during LP Peak at DP onset followed by sudden decrease and return to baseline
Smriga et al (2000) a [102]	Rats	7h–19h	26h	Ventral Hypothalamus	Higher during DP, lower during LP
Kalen et al (1989) [82]	Rats	12:12	24h	Caudal Hippocampus	Higher during DP, lower during LP
Drijfhout et al (1996) [103]	Rats	6h–18h	16h	Pineal gland	Peak 1–3h after DP onset, decrease 2h before LP Higher during DP, lower during LP
Morien et al (1995) B [100]*	Rats	7h–19h	24h	Septal Nuclei and the Ventromedial Thalamus	Stable

[i] Each row represents one study (i.e. an experimental group within a publication) and a qualitative description of the results. Fluctuations are described as “higher” and “lower” disregarding actual magnitudes of changes. Rows are sorted by brain region. Lower case letters indicate separate publications from the same authors in the same year; upper cases letters represent separate groups within publications; numbers represent separate brain regions within animals. *These studies provided average monoamine concentrations pooled for several brain regions.

Abbreviations: L/D Cycle: Light-Dark Cycle; LP: Light Phase; DP: Dark phase.

Table 6

Circadian rhythms in adrenaline levels.

Adrenaline-Circadian Rhythms
Reference_ID	Animals	L/D Cycle	Duration	Brain Region	Adrenaline Levels
Robinson et al (1991) [57]	Sheep	Natural cycle	20h	Preoptic Area	Stable

[i] Abbreviations: L/D Cycle: Light/Dark Cycle; DP: Dark-Phase; LP: Light-Phase.

Table 7

Dopamine levels during naturally occurring sleep stages.

Dopamine-Sleep
Reference	Animals	L/D Cycle	Brain Region	Dopamine Levels
Orosco et al (1995) [104]	Rats	6h–18h	PVN/VMN	2 days measurement with different observation Day1: W and REM high, SWS lower/ Day2: W and REM low with SWS high
Nicolaidis et al (2001) A [105]	Rats	?	PVN/VMN	Levels increases from SWS to REM and from REM to W. Levels decreases from W to SWS
Shouse et al (2000) a 1 [106]	Cats	?	Amygdala	Stable during all stages (AW, QW, SWS and REM)
Shouse et al (2001) a 1 [107]	Cats	?	Amygdala	Stable during wake and sleep
Shouse et al (2001) b 1 [108]	Cats	?	Amygdala	Stable during wake and sleep
Shouse et al (2000) a 2 [106]	Cats	?	Locus Coeruleus	Stable during all stages (AW, QW, SWS and REM)
Shouse et al (2001) a 1 [107]	Cats	?	Locus Coeruleus	Stable during wake and sleep
Shouse et al (2001) b 2 [108]	Cats	?	Locus Coeruleus	Stable during wake and sleep
Lena et al (2005) 1 [109]	Rats	8h–20h	Medial Prefrontal Cortex	W: high level, SWS: low level, REM: in between
De Saint Hilaire (2000) [110]	Rats	6h–18h	Prefrontal Cortex	W: lower, SWS: high. Higher in REM when followed by W
Nicolaidis et al (2001) B [105]	Rats	?	Prefrontal Cortex	W to SWS: decrease, SWS to W: increases
Lena et al (2005) 2 [109]	Rats	8h–20h	Nucleus Accumbens	W and REM: high, SWS: low

[i] Each row represents one study (i.e. an experimental group within a publication) and a qualitative description of the results. Fluctuations are described as “higher” and “lower” disregarding actual magnitudes of changes. Rows are sorted by brain region. Lower case letters indicate separate publications from the same authors in the same year; upper cases letters represent separate groups within publications; numbers represent separate brain regions within animals.

Abbreviations: W: Wake; SWS: Slow Wave Sleep; REM: Rapid Eye Movements Sleep; PVN: Paraventricular Nucleus; VMN: Ventromedial Hypothalamic Nucleus.

Table 8

DOPAC levels during naturally occurring sleep stages.

DOPAC-Sleep
Reference	Animals	L/D Cycle	Brain Region	DOPAC Levels
De Saint Hilaire (2000) [110]	Rats	6h–18h	Prefrontal Cortex	Stable
Orosco et al (1995) [104]	Rats	6h–18h	PVN/VMN	W: low, SWS: intermediate, REM: high
Nicolaidis et al (2001) A [105]	Rats	?	PVN/VMN	From SWS to W: decrease, from SWS to REM: increase, from REM to W: increase

[i] Each row represents one study (i.e. an experimental group within a publication) and a qualitative description of the results. Fluctuations are described as “higher” and “lower” disregarding actual magnitudes of changes. Rows are sorted by brain region. Lower case letters indicate separate publications from the same authors in the same year; upper cases letters represent separate groups within publications; numbers represent separate brain regions within animals.

Abbreviations: DOPAC: 3,4–Dihydroxyphenylacetic acid; W: Wake; SWS: Slow Wave Sleep; REM: Rapid Eye Movements Sleep; PVN: Paraventricular Nucleus; VMN: Ventromedial Hypothalamic Nucleus.

Table 9

Serotonin levels during naturally occurring sleep stages.

Serotonin-Sleep
Reference	Animals	L/D Cycle	Brain Region	Serotonin Levels
Orosco et al (1995) [104]	Rats	6h–18h	PVN/VMN	W: high, SWS: intermediate, REM: low
Nicolaidis et al (2001) A [105]	Rats	?	PVN/VMN	W: high, SWS: low
Wilkinson et al (1991) [111]	Cats	?	Preoptic Area/Anterior Hypothalamus	W: high, SWS: low
Python et al (2001) [112]	Rats	8h–20h	Preoptic Area	W: high, SWS: intermediate, REM: low. SWS after REM showed no strong fluctuation, but when W after REM levels showed a strong increase
Shouse et al (2000) a 1 [106]	Cats	?	Amygdala	W: high, SWS: intermediate, REM: low
Shouse et al (2001)a 1 [107]	Cats	?	Amygdala	W: high, SWS: low
Shouse et al (2001) b 1 [108]	Cats	?	Amygdala	W: high, SWS: intermediate, REM: low
Shouse et al (2000) a 2 [106]	Cats	?	Locus Coeruleus	W: high, SWS: intermediate, REM: low
Shouse et al (2001) a 2 [107]	Cats	?	Locus Coeruleus	W: high, SWS: low
Shouse et al (2001) b 1 [108]	Cats	?	Locus Coeruleus	W: high, SWS: intermediate, REM: low
Park et al (1999) [113]	Rats	7h–19h	Posterior Hippocampus	W: high, SWS and REM: low
Gronli et al (2007) [114]	Rats	7h–19h	Hippocampus	W and SWS: high, REM: low
Bjorvatn et al (2002) A1 [115]	Rats	6h–18h	Ventral Hippocampus	W: high, Sleep: low
Penalva et al (2003) A [116]	Rats	7h30–19h30	Dorsal Hippocampus	W: high, SWS: low, REM: low
Fiske et al (2006) 1 [117]	Rats	6h–18h	Dorsal Raphe	W: high, SWS and REM: low
Fiske et al (2008) 1 [118]	Rats	6h–18h	Dorsal Raphe	W: high, SWS and REM: low
Portas et al (1994) [119]	Cats	Constant light	Dorsal Raphe	W: high, SWS: intermediate, REM: low
Portas et al (1996) [120]	Cats	Constant light	Dorsal Raphe	W: high, SWS: intermediate, REM: low
Portas et al (1998) 1 [121]	Rats	6h–18h	Dorsal Raphe	W: high, SWS: intermediate, REM: low
De Saint Hilaire et al (2000) [110]	Rats	6h–18h	Prefrontal Cortex	W: high, SWS: intermediate, REM: low. Except, 5–HT increases in REM if followed by W
Nicolaidis et al (2001) B [105]	Rats	?	Prefrontal Cortex	W increases before a SWS stage. From SWS to W decrease after a long SWS period.
Portas et al (1998) 2 [121]	Rats	6h–18h	Frontal cortex	W: high, SWS: intermediate, REM: low
Mukaida et al (2007) [122] Ɨ	Rats	7h–19h	Frontal cortex	W: high, SWS: lower
Fiske et al (2008) 2 [118]	Rats	6h–18h	Frontal cortex	Stable
Bjorvatn et al (2002) A2 [115]	Rats	6h–18h	Frontal cortex	W: high, Sleep: low
Zeitzer et al (2002) [41]	Human	L/D cycle of the season	Lateral Ventricle	W: high, SWS: intermediate, REM: low From stage 2 to REM: decrease/from REM to stage 2: increase
McCarley et al (2004) [123]	?	?	PPT	W: high, SWS: intermediate, REM: low
Strecker et al (1999) [124]	Cats	?	PPT	W: high, SWS: intermediate, REM: low
Fiske et al (2006) 2 [117]	Rats	6h–18h	Frontal cortex	W: high, SWS: low, REM: intermediate
Lapierre et al (2012) [125]	Seals	?	Cortex	W: high, SWS: intermediate, REM: low
Lapierre et al (2013) a [126]	Seals	8h–20h	Cerebral cortex	W: high, BSWS: the lowest, REM: low
Lyamin et al (2016) A [127]*	Seals	8h–20h	Occipital cortex and Frontal cortex	W: high, SWS: intermediate, REM: low. Same decrease was seen in seals specific sleep stages (USWS (right and left), BSWS)
Blanco-Centurion et al (2001) A [128]	Rats	8h–20h	Gigantocellular reticular nucleus	W: high, SWS: intermediate, REM: low
Iwakiri et al (1993) [129]	Cats	?	Medial Pontine Reticular Formation	W: high, SWS: intermediate, REM: low
Lyamin et al (2016) C [127]	Seals	8h–20h	Thalamus	W: high, SWS: intermediate, REM: low
Lyamin et al (2016) D [127]	Seals	8h–20h	Caudate nucleus	W: high, SWS: intermediate, REM: low

[i] Each row represents one study (i.e. an experimental group within a publication) and a qualitative description of the results. Fluctuations are described as “higher” and “lower” disregarding actual magnitudes of changes. Rows are sorted by brain region. Lower case letters indicate separate publications from the same authors in the same year; upper cases letters represent separate groups within publications; numbers represent separate brain regions within animals. Ɨ Anaesthesia was applied during baseline: 6 L/min mixture of 25% oxygen and75% nitrogen. All the other studies measured natural sleep. *These studies provided average monoamine concentrations pooled for several brain regions.

Abbreviations: W: Wake; SWS: Slow Wave Sleep; REM: Rapid Eye Movements Sleep; PVN: Paraventricular Nucleus; VMN: Ventromedial Hypothalamic Nucleus; PPT: Pedunculopontine Tegmental Nucleus.

Table 10

5-HIAA levels during naturally occurring sleep stages.

5-HIAA-Sleep
Reference	Animals	L/D Cycle	Brain Region	5-HIAA Levels
De Saint Hilaire (2000) [110]	Rats	6h–18h	Prefrontal Cortex	Stable
Orosco et al (1995) [104]	Rats	6h–18h	PVN/VMN	1^st day: W: intermediate, SWS: low, REM: high 2^nd day: W: high, SWS: intermediate, REM: low
Nicolaidis et al (2001) A [105]	Rats	?	PVN/VMN	W: High, Sleep: Lower. W is lower if preceded by REM.
Portas et al (1994) [119]	Cats	Constant light	Dorsal Raphe	Stable
Iwakiri et al (1993) [129]	Cats	?	Medial Pontine Reticular Formation	Stable

[i] Each row represents one study (i.e. an experimental group within a publication) and a qualitative description of the results. Fluctuations are described as “higher” and “lower” disregarding actual magnitudes of changes. Rows are sorted by brain region. Lower case letters indicate separate publications from the same authors in the same year; upper cases letters represent separate groups within publications; numbers represent separate brain regions within animals.

Abbreviations: 5-HIAA: 5-hydroxyindoleacetic acid; W: Wake; SWS: Slow Wave Sleep; REM: Rapid Eye Movements Sleep; PVN: Paraventricular Nucleus; VMN: Ventromedial Hypothalamic Nucleus.

Table 11

Noradrenaline levels during naturally occurring sleep stages.

Noradrenaline-Sleep
Reference	Animals	L/D Cycle	Brain Region	Noradrenaline Levels
Orosco et al (1995) [104]	Rats	6h–18h	PVN/VMN	1^st day: W: high, SWS: low, REM: intermediate 2^nd day W: high, SWS: intermediate, REM: low
Nicolaidis et al (2001) A [105]	Rats	?	PVN/VMN	W: high, SWS: intermediate, REM: low. If SWS followed by W or REM: increase, while if REM or W is followed by SWS: decrease
Lyamin et al (2016) B [127]	Seals	8h–20h	Hypothalamus	W: high, SWS: intermediate, REM: low
Shouse et al (2000) a 1 [106]	Cats	?	Amygdala	W: high, SWS: intermediate, REM: low
Shouse et al (2000) b 1 [130]	Cats	?	Amygdala	W: high, SWS: low
Shouse et al (2001) a 1 [107]	Cats	?	Amygdala	W: high, SWS: low
Shouse et al (2001) b 1 [108]	Cats	?	Amygdala	W: high, SWS: intermediate, REM: low
Park et al (2002) [131]	Rats	7h–19h	Amygdala	W: high, SWS: low, REM: lower
Shouse et al (2000) a 2 [106]	Cats	?	Locus Coeruleus	W: high, SWS: intermediate, REM: low
Shouse et al (2000) b 2 [130]	Cats	?	Locus Coeruleus	W: high, Sleep: low
Shouse et al (2001) a 2 [107]	Cats	?	Locus Coeruleus	W: high, Sleep: low
Shouse et al (2001) b 2 [108]	Cats	?	Locus Coeruleus	W: high, SWS: intermediate, REM: low
Bellesi et al (2016) A1	Mice	8h–20h	Medial Prefrontal Cortex	W: high, Sleep: low
Lena et al (2005) 1 [109]	Rats	8h–20h	Medial Prefrontal Cortex	W: high, SWS: intermediate, REM: low
De Saint Hilaire et al (2000) [110]	Rats	6h–18h	Prefrontal Cortex	W: lower, SWS: high (relatively stable)
Lena et al (2005) 2 [109]	Rats	8h–20h	Nucleus Accumbens	W: high, SWS: intermediate, REM: low
Lapierre et al (2013) b [132]	Seals	?	Cortex	W: high, SWS: intermediate, REM: low.
Lyamin et al (2016) A [127]*	Seals	8h–20h	Occipital cortex, frontal cortex	W: high, SWS: intermediate, REM: low. Same decrease was seen in seals specific sleep stages (USWS (right and left), BSWS)
Bellesi et al (2016) A2	Mice	8h–20h	M1	W: high, Sleep: low

[i] Each row represents one study (i.e. an experimental group within a publication) and a qualitative description of the results. Fluctuations are described as “higher” and “lower” disregarding actual magnitudes of changes. Rows are sorted by brain region. Lower case letters indicate separate publications from the same authors in the same year; upper cases letters represent separate groups within publications; numbers represent separate brain regions within animals. * These studies provided average monoamine concentrations pooled for several brain regions.

Abbreviations: W: Wake; SWS: Slow Wave Sleep; REM: Rapid Eye Movements Sleep; PVN: Paraventricular Nucleus; VMN: Ventromedial Hypothalamic Nucleus; M1: Primary Motor Cortex.

Table 12

Dopamine and sleep deprivation.

Dopamine-SD
Reference_ID	Animals	SD Methods	Duration	Brain Region	Dopamine levels during/after SD
Murillo-Rodriguez et al (2016) [134]	Rats	-Stroking fur with paint brush -Light noise in the cage -Tapping -Placing object in the cage	6h	Nucleus Accumbens	Increase after SD

[i] Each row represents one study (i.e. an experimental group within a publication) and a qualitative description of the results. Abbreviation: SD: Sleep Deprivation.

Table 13

DOPAC and sleep deprivation.

DOPAC-SD
Reference_ID	Animals	SD Methods	Duration	Brain Region	DOPAC levels during/after SD
Zant et al (2010) [135]	Rats	Gentle handling	6h	Basal Forebrain	Increase during SD, decrease to baseline levels during sleep recovery
Zant et al (2011) [136]	Rats	-Gentle handling including placing objects in the cage	6h	Basal Forebrain	Increase during 3 first hours of SD, then plateau. It decreases to baseline levels during sleep recovery

[i] Each row represents one study (i.e. an experimental group within a publication) and a qualitative description of the results.

Abbreviations: DOPAC: 3,4-Dihydroxyphenylacetic acid; SD: Sleep Deprivation.

Table 14

Serotonin and sleep deprivation.

Serotonin-SD
Reference_ID	Animals	SD Methods	Duration	Brain Region	Serotonin levels during/after SD
Bjorvatn et al (2002) B1 [115]	Rats	-Gentle sensory stimulation (knocking on the plexiglas door, opening the door, gentle handling)	8h30	Ventral hippocampus	Decrease during SD
Lopez-Rodriguez et al (2003) a [80]	Rats	Modified disk-over-water	24h	Posterior Hippocampus	Increase during SD and remain high during recovery
Lopez-Rodriguez et al (2003) b [133]	Rats	Small platform (6cm) in tank filled with water (REM deprivation)	24h but measurement for 11h	Posterior Hippocampus	Increase during SD and decrease below baseline during recovery
Penalva et al (2003) B [116]	Rats	-Introducing or removing objects -Shaking the cage slightly	4h	Dorsal hippocampus	Increase during SD. During recovery time, levels are high during W and low during REM sleep.
Penalva et al (2003) C [116]	Rats	-Introducing or removing objects -Shaking the cage slightly	4h	Dorsal hippocampus	Increase during SD. During recovery time, levels are high during W and low during REM sleep.
Bjorvatn et al (2002) B2 [115]	Rats	-Gentle sensory stimulation (knocking on the plexiglas door, opening the door, handling)	8h30	Frontal Cortex	Decrease during SD
Blanco-Centurion et al (2001) B [128]	Rats	Platform (6.5cm) surrounded by water (REM deprivation)	92h	Gigantoreticular Cellular Nucleus	Decrease (factor 100) during SD and remain low during recovery
Grossman et al (2000) B [75]	Hamsters	-Continuous gentle handling -Light puffs of air	3h (red dim light)	Lateral Margin of SCN	Increase during SD, decreases during recovery but slight increase at the end.
Grossman et al (2000) C [75]	Hamsters	-Continuous handling-Light puffs of air	3h	Lateral Margin of SCN	Increase during SD, highest peak at the end of SD. Decreases to baseline levels during recovery
Murillo-Rodriguez et al (2016) [134]	Rats	-Stroking fur with paint brush-Light noise in the cage-Tapping-Placing object in the cage	6h	Nucleus Accumbens	Increase after SD

[i] Each row represents one study (i.e. an experimental group within a publication) and a qualitative description of the results. Rows are sorted by brain region.

Lower case letters indicate separate publications from the same authors in the same year; upper cases letters represent separate groups within publications; numbers represent separate brain regions within animals.

Abbreviations: SD: Sleep Deprivation; SCN: Suprachiasmatic Nucleus.

Table 15

5-HIAA and sleep deprivation.

5-HIAA-SD
Reference_ID	Animals	SD Methods	Duration	Brain Region	5-HIAA levels during/after SD
Zant et al (2010) [135]	Rats	Gentle handling	6h	Basal Forebrain	Increase during SD and return to baseline level during recovery
Zant et al (2011) [136]	Rats	-Gentle handling -Placing object in the cage	6h	Basal Forebrain	Increase during SD and return to baseline level during recovery
Blanco-Centurion et al (2001) B [128]	Rats	Platform (6.5cm) surrounded by water (REM deprivation)	92h	Gigantoreticular Cellular Nucleus	Decrease during SD, and increase during recovery

[i] Each row represents one study (i.e. an experimental group within a publication) and a qualitative description of the results. Rows are sorted by brain region.

Lower case letters indicate separate publications from the same authors in the same year; upper cases letters represent separate groups within publications; numbers represent separate brain regions within animals.

Abbreviations: SD: Sleep Deprivation; 5-HIAA: 5-Hydroxyindoleacetic acid.

Table 16

Noradrenaline and sleep deprivation.

Noradrenaline-SD
Reference_ID	Animals	SD Methods	Duration	Brain Region	Noradrenaline levels during/after SD
Bellesi et al (2016) B1	Mice	-Exposure to novel objects	6h	Medial Prefrontal Cortex	Increase during SD and slightly decrease at the end
Bellesi et al (2016) B2	Mice	-Exposure to novel objects	6h	M1	Increase during SD
Murillo-Rodriguez et al (2016) [134]	Rats	-Stroking fur with paint brush -Light noise in the cage-Tapping-Placing object in the cage	6h	Nucleus Accumbens	Increase after SD

[i] Each row represents one study (i.e. an experimental group within a publication) and a qualitative description of the results. Rows are sorted by brain region.

Lower case letters indicate separate publications from the same authors in the same year; upper cases letters represent separate groups within publications; numbers represent separate brain regions within animals.

Abbreviations: SD: Sleep Deprivation; M1: Primary Motor Cortex.

Table 17

Adrenaline and sleep deprivation.

Adrenaline-SD
Reference_ID	Animals	SD Methods	Duration	Brain Region	Adrenaline levels during/after SD
Murillo-Rodriguez et al (2016) [134]	Rats	-Stroking fur with painting brush-Light noise during the cage-Tapping-Placing object in the cage	6h	Nucleus Accumbens	Increase after SD

[i] Abbreviations: SD: Sleep Deprivation.

Network meta-analysis comparing serotonin levels during wakefulness, SWS and REM sleep.
This plot summarises the results of 26 studies; 19 had data for each stage, 7 had data only for wakefulness and SWS. For the overall effect, p < 0.0001. The analysis shows significant heterogeneity; Τ² = 0.0059; I² = 98.4%.
Abbreviations: SWS: Slow Wave Sleep; REM: Rapid Eye Movement sleep.

Network meta-analysis of noradrenaline levels during wakefulness, SWS and REM sleep.
This plot summarises the results of 13 studies; 8 had data for each stage, 5 had data only for wakefulness and SWS. For the overall effect p < 0.0001. The analysis shows significant heterogeneity; Τ² = 0.7835; I² = 99.5%.
Abbreviations: SWS: Slow Wave Sleep; REM: Rapid Eye Movement sleep.

Table 18

Summary of medians, interquartile ranges and Friedman’s ANOVA test statistics for each compound analysed during the different phases of the experiment.

Analyte	Phase	Median (nmol/L)	IQR 25%	IQR 75%	Test statistics
5-HT	Light	1.56	1.17	6.88	χ²(3) = 5.694 p = 0.127
5-HT	Dark	0.92	0.61	2.21	χ²(3) = 5.694 p = 0.127
SD	0.96	0.37	1.67
Recovery	1.19	0.44	4.60
5-HIAA	Light	86.67	61.21	60.71	χ²(3) = 6.60 p = 0.086
5-HIAA	Dark	42.56	20.80	98.86	χ²(3) = 6.60 p = 0.086
SD	103.32	72.68	55.56
Recovery	104.07	86.46	33.14
5-HTP	Light	2.17	0.35	2.21	χ²(3) = 4.92 p = 0.178
5-HTP	Dark	1.57	0.24	1.45	χ²(3) = 4.92 p = 0.178
SD	2.43	0.46	0.95
Recovery	1.20	0.89	1.23
DA	Light	0.49	0.19	0.15	χ²(3) = 5.40 p = 0.145
DA	Dark	0.26	0.12	0.12	χ²(3) = 5.40 p = 0.145
SD	0.34	0.10	0.22
Recovery	0.30	0.15	0.12
DOPAC	Light	2.10	0.97	2.47	χ²(3) = 8.846 p = 0.037
DOPAC	Dark	1.70	0.67	3.35	χ²(3) = 8.846 p = 0.037
SD	2.06	0.84	4.70
Recovery	1.33	0.36	1.36
NA	Light	0.28	0.14	1.00	χ²(3) = 7.145 p = 0.067
NA	Dark	0.47	0.300	0.38	χ²(3) = 7.145 p = 0.067
SD	0.31	0.19	0.44
Recovery	0.11	0.01	0.09
ADRE	Light	0.18	0.06	0.04	χ²(3) = 1.8 p = 0.615
ADRE	Dark	0.21	0.10	0.06	χ²(3) = 1.8 p = 0.615
SD	0.28	0.14	0.15
Recovery	0.23	0.11	0.09

[i] Friedman’s ANOVA’s were performed to compare concentrations (nmol/L) between the different phases. For 5-HT, light phase n = 7, dark phase and SD n = 8, and recovery n = 9. For 5-HIAA, light phase, dark phase, and SD n = 11, recovery n = 10. For 5-HTP, light phase n = 9, dark phase, SD, and recovery n = 8. For dopamine, all phases n = 11. For DOPAC, light phase and recovery n = 9, dark phase n = 7, SD n = 8. For noradrenaline, all phase n = 11. For adrenaline, light phase, SD and recovery n = 10, dark phase n = 9. Numbers of observations vary because of missing samples (temporarily obstructed flow) and some concentrations being below HPLC detection limits.

Abbreviations: 5-HT: Serotonin; 5-HIAA: 5-Hydroxyindoleacetic Acid; 5-HTP: 5-Hydroxytryptophan; DA: Dopamine; DOPAC: 3,4-Dihydroxyphenylacetic acid; NA: Noradrenaline; ADRE: Adrenaline; IQR: Inter Quartile Range.

Median DOPAC dialysates concentrations in (nM) ± inter quartile range.
Light: 12h of baseline during the light phase; dark: 12h of baseline during the dark phase; SD: 12h of sleep deprivation during the light phase and rec: recovery for 12h. *Wilcoxon signed rank test: T = 0, p = 0.018.

Brain Microdialysate Monoamines in Relation to Circadian Rhythms, Sleep, and Sleep Deprivation – a Systematic Review, Network Meta-analysis, and New Primary Data

Figures & Tables

Figure 1

Table 1

Table 2

Table 3

Table 4

Table 5

Table 6

Table 7

Table 8

Table 9

Table 10

Table 11

Table 12

Table 13

Table 14

Table 15

Table 16

Table 17

Figure 2

Figure 3

Table 18

Figure 4

Paradigm

My account