title: Global depletion of dopamine using intracerebroventricular 6-hydroxydopamine injection disrupts normal circadian wheel-running patterns and PERIOD2 expression in the rat forebrain.
abstract: Normal circadian rhythms of behavior are disrupted in disorders involving the dopamine (DA) system, such as Parkinson's disease. We have reported previously using unilateral injections of the catecholamine toxin, 6-hydroxydopamine (6-OHDA), into the medial forebrain bundle that DA signaling regulates daily expression of the clock protein, PERIOD2 (PER2), in the dorsal striatum of the rat. In the present study, we made widespread lesions of DA fibers using large injections of 6-OHDA into the third ventricle to determine the involvement of DA in normal daily rhythms of wheel-running activity and PER2 patterns in the suprachiasmatic nucleus (SCN) and several regions of the limbic forebrain. Rats injected with 6-OHDA and housed in constant darkness were less active in the wheel and showed a disorganized pattern of activity in which wheel running was not confined to a specific phase over 24 h. The 6-OHDA injection had no effect on the daily PER2 pattern in the SCN, but blunted the normal rise in PER2 in the dorsal striatum. 6-OHDA also blunted PER2 expression in the periventricular nucleus of the hypothalamus, a region in which a daily PER2 pattern has not been previously reported in male rats, and in the oval nucleus of the bed nucleus of the stria terminalis, but not in the central nucleus of the amygdala. These results indicate that DA plays a prominent role in regulating circadian activity at both behavioral and molecular levels.
authors.affiliation: Center for Studies in Behavioral Neurobiology/Centre de Recherche en Neurobiologie Comportementale, Concordia University, 7141 Sherbrooke Street West, Montreal, QC H4B 1R6, Canada.
authors.forename: Luciana
authors.initials: L
authors.lastname: Gravotta
authors.forename: Alex M
authors.initials: AM
authors.lastname: Gavrila
authors.forename: Suzanne
authors.initials: S
authors.lastname: Hood
authors.forename: Shimon
authors.initials: S
authors.lastname: Amir
mesh_terms: D018663:Adrenergic Agents / Q000008:administration & dosage / Q000494:pharmacology; D000818:Animals; D002940:Circadian Rhythm / Q000187:drug effects*; D004298:Dopamine / Q000378:metabolism*; D057967:Infusions, Intraventricular; D008032:Limbic System / Q000033:anatomy & histology / Q000187:drug effects* / Q000502:physiology; D008297:Male; D009043:Motor Activity / Q000187:drug effects*; D016627:Oxidopamine / Q000008:administration & dosage* / Q000494:pharmacology*; D056950:Period Circadian Proteins / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar
chemical_list: D018663:Adrenergic Agents; C513311:Per2 protein, rat; D056950:Period Circadian Proteins; D016627:Oxidopamine; D004298:Dopamine