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Glycogen synthase kinase‐3 β in the ventral tegmental area mediates diurnal variations in cocaine‐induced conditioned place preference in rats
Author(s) -
Li SuXia,
Wei YiMing,
Shi HaiShui,
Luo YiXiao,
Ding ZengBo,
Xue YanXue,
Lu Lin,
Yu ChangXi
Publication year - 2014
Publication title -
addiction biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.445
H-Index - 78
eISSN - 1369-1600
pISSN - 1355-6215
DOI - 10.1111/adb.12068
Subject(s) - ventral tegmental area , conditioned place preference , circadian rhythm , gsk 3 , medicine , endocrinology , prefrontal cortex , brain stimulation reward , neuroscience , psychology , pharmacology , biology , dopamine , nucleus accumbens , phosphorylation , microbiology and biotechnology , cognition , dopaminergic
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‐3 β ( GSK ‐3 β ) 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 ‐3 β activity in the SCN and reward‐related brain areas; and (4) the effect of the GSK ‐3 β inhibitor SB 216763 microinjected bilaterally into the ventral tegmental area ( VTA ) on cocaine‐induced CPP . A significant diurnal rhythm of GSK ‐3 β activity was found in the SCN and reward‐related brain areas, with diurnal variations in cocaine‐induced CPP . GSK ‐3 β activity in the SCN and reward‐related brain areas exhibited marked diurnal variations in rats treated with saline. GSK ‐3 β activity in rats treated with cocaine exhibited distinct diurnal variations only in the prefrontal cortex and VTA . Cocaine decreased the expression of phosphorylated GSK ‐3 β (i.e. increased GSK ‐3 β activity) only in the VTA in rats trained and tested at ZT 4 and ZT 16. SB 216763 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 ‐3 β may be a regulator of diurnal variations in cocaine‐induced CPP .