title: Glycogen synthase kinase-3β in the ventral tegmental area mediates diurnal variations in cocaine-induced conditioned place preference in rats.
abstract: Cocaine sensitization and reward are reported to be under the influence of diurnal rhythm. However, no previous studies have reported brain areas that play a role as modulators and underlie the mechanism of diurnal variations in cocaine reward. We examined (1) the diurnal rhythm of glycogen synthase kinase-3β (GSK-3β) activity in the suprachiasmatic nucleus (SCN) and reward-related brain areas in naive rats; (2) the effect of day and night on the acquisition of cocaine-induced conditioned place preference (CPP); (3) the influence of cocaine-induced CPP on GSK-3β activity in the SCN and reward-related brain areas; and (4) the effect of the GSK-3β inhibitor SB216763 microinjected bilaterally into the ventral tegmental area (VTA) on cocaine-induced CPP. A significant diurnal rhythm of GSK-3β activity was found in the SCN and reward-related brain areas, with diurnal variations in cocaine-induced CPP. GSK-3β activity in the SCN and reward-related brain areas exhibited marked diurnal variations in rats treated with saline. GSK-3β activity in rats treated with cocaine exhibited distinct diurnal variations only in the prefrontal cortex and VTA. Cocaine decreased the expression of phosphorylated GSK-3β (i.e. increased GSK-3β activity) only in the VTA in rats trained and tested at ZT4 and ZT16. SB216763 microinjected into the VTA bilaterally eliminated the diurnal variations in cocaine-induced CPP, but did not affect the acquisition of cocaine-induced CPP. These findings suggest that the VTA may be a critical area involved in the diurnal variations in cocaine-induced CPP, and GSK-3β may be a regulator of diurnal variations in cocaine-induced CPP.
authors.affiliation: National Institute on Drug Dependence, Peking University, China.
authors.forename: Su-Xia
authors.initials: SX
authors.lastname: Li
authors.forename: Yi-Ming
authors.initials: YM
authors.lastname: Wei
authors.forename: Hai-Shui
authors.initials: HS
authors.lastname: Shi
authors.forename: Yi-Xiao
authors.initials: YX
authors.lastname: Luo
authors.forename: Zeng-Bo
authors.initials: ZB
authors.lastname: Ding
authors.forename: Yan-Xue
authors.initials: YX
authors.lastname: Xue
authors.forename: Lin
authors.initials: L
authors.lastname: Lu
authors.forename: Chang-Xi
authors.initials: CX
authors.lastname: Yu
mesh_terms: D000818:Animals; D002940:Circadian Rhythm / Q000187:drug effects; D003042:Cocaine / Q000494:pharmacology*; D003213:Conditioning, Psychological / Q000187:drug effects*; D018765:Dopamine Uptake Inhibitors / Q000494:pharmacology*; D038362:Glycogen Synthase Kinase 3 / Q000502:physiology*; D007211:Indoles / Q000494:pharmacology; D008297:Male; D008301:Maleimides / Q000494:pharmacology; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D017207:Rats, Sprague-Dawley; D012201:Reward; D013493:Suprachiasmatic Nucleus / Q000201:enzymology; D017557:Ventral Tegmental Area / Q000187:drug effects / Q000201:enzymology*
chemical_list: D018765:Dopamine Uptake Inhibitors; D007211:Indoles; D008301:Maleimides; D047428:Protein Kinase Inhibitors; C417521:SB 216763; D038362:Glycogen Synthase Kinase 3; D003042:Cocaine
keywords: Cocaine; GSK-3β; SB216763; conditioned place preference; diurnal rhythm