title: Increases in extracellular serotonin and dopamine metabolite levels in the basal forebrain during sleep deprivation.
abstract: The basal forebrain (BF) is an important mediator of cortical arousal, which is innervated by all ascending arousal systems. During sleep deprivation (SD) a site-specific accumulation of sleep factors in the BF results in increased sleep pressure (Kalinchuk et al., 2006; Porkka-Heiskanen et al., 1997; Porkka-Heiskanen et al., 2000). However, animals are able to stay awake and even increase their neuronal activity in the BF and cortex during SD, suggesting increased activity of the ascending arousal systems to counteract the effect of sleep pressure. This study used in vivo microdialysis to measure the effect of a 6h SD, by "gentle handling" in freely moving rats, on the extracellular levels of serotonin and dopamine metabolites (5-HIAA, and DOPAC and HVA respectively) in the BF. Additionally, because glucocorticoids can interact with monoaminergic neurotransmission, and SD could be stressful, corticosterone levels were measured. We found an increase in extracellular serotonin and dopamine metabolite levels (n=8, p≤0.05). No interaction between corticosterone and the monoaminergic systems was apparent. Extracellular corticosterone levels showed no increase during the first 3h of SD, and the subsequent increase (n=8, p≤0.05) did not result in values exceeding the normal diurnal maximum, indicating that no substantial stress was induced. The results demonstrate that SD increases extracellular dopamine and serotonin metabolites in the BF, suggesting increased activity of the ascending arousal systems. It remains to be investigated what the specific roles of the dopaminergic and serotonergic ascending arousal systems are in BF-mediated cortical arousal.
authors.affiliation: Institute of Biomedicine, Physiology, University of Helsinki, Helsinki, Finland.
authors.forename: J C
authors.initials: JC
authors.lastname: Zant
authors.forename: C H C
authors.initials: CH
authors.lastname: Leenaars
authors.forename: A
authors.initials: A
authors.lastname: Kostin
authors.forename: E J W
authors.initials: EJ
authors.lastname: Van Someren
authors.forename: T
authors.initials: T
authors.lastname: Porkka-Heiskanen
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D002851:Chromatography, High Pressure Liquid / Q000379:methods; D003345:Corticosterone / Q000378:metabolism; D004298:Dopamine / Q000378:metabolism*; D004569:Electroencephalography / Q000379:methods; D045604:Extracellular Fluid / Q000378:metabolism*; D008297:Male; D017551:Microdialysis / Q000379:methods; D016548:Prosencephalon / Q000166:cytology / Q000378:metabolism*; D011863:Radioimmunoassay / Q000379:methods; D051381:Rats; D017208:Rats, Wistar; D012701:Serotonin / Q000378:metabolism*; D012892:Sleep Deprivation / Q000473:pathology* / Q000503:physiopathology
chemical_list: D012701:Serotonin; D004298:Dopamine; D003345:Corticosterone