Neural correlates of sleepiness induced by catecholamine depletion

• Published in: Psychiatry research. Neuroimaging 2011-10, Vol.194 (1), p.73-78
• Main Authors: Meyers, Noah, Fromm, Stephen, Luckenbaugh, David A, Drevets, Wayne C, Hasler, Gregor
• Format: Article
• Language: English
• Subjects: Adolescent; Adult; Amphetamine - administration & dosage; Biological and medical sciences; Brain - diagnostic imaging; Brain - drug effects; Brain - pathology; Brain Mapping; Catecholamines - deficiency; Central Nervous System Stimulants - administration & dosage; Cross-Over Studies; Dopamine; Double-Blind Method; Female; Fluorodeoxyglucose F18; Humans; Hypothalamus; Male; Medical sciences; Mesencephalon; Middle Aged; Norepinephrine; Positron-Emission Tomography - methods; Prolactin; Psychiatry; Psychology. Psychoanalysis. Psychiatry; Psychopathology. Psychiatry; Radiology; Sleep; Sleep Initiation and Maintenance Disorders - diagnostic imaging; Sleep Initiation and Maintenance Disorders - etiology; Sleep Initiation and Maintenance Disorders - pathology; Young Adult
• ISSN: 0925-4927; 1872-7506
• DOI: 10.1016/j.pscychresns.2011.06.015

Abstract Although extensive indirect evidence exists to suggest that the central dopaminergic system plays a significant role in the modulation of arousal, the functional effect of the dopaminergic influence on the regulation of the sleep–wake cycle remains unclear. Thirteen healthy volunteers and 15 unmedicated subjects with a history of major depressive disorder underwent catecholamine depletion (CD) using oral alpha-methyl-para-tyrosine in a randomized, placebo-controlled, double-blind, crossover study. The main outcome measures in both sessions were sleepiness (Stanford-Sleepiness-Scale), cerebral glucose metabolism (positron emission tomography), and serum prolactin concentration. CD consistently induced clinically relevant sleepiness in both groups. The CD-induced prolactin increase significantly correlated with CD-induced sleepiness but not with CD-induced mood and anxiety symptoms. CD-induced sleepiness correlated with CD-induced increases in metabolism in the medial and orbital frontal cortex, bilateral superior temporal cortex, left insula, cingulate motor area and in the vicinity of the periaqueductal gray. This study suggests that the association between dopamine depletion and sleepiness is independent of the brain reward system and the risk for depression. The visceromotor system, the cingulate motor area, the periaqueductal gray and the caudal hypothalamus may mediate the impact of the dopaminergic system on regulation of wakefulness and sleep.