RRC ID 32722
Author Hu Z, Oh EH, Chung YB, Hong JT, Oh KW.
Title Predominant D1 Receptors Involvement in the Over-expression of CART Peptides after Repeated Cocaine Administration.
Journal Korean J Physiol Pharmacol
Abstract The aim of this study was to investigate the involvement of dopaminergic receptors (DR) in behavioral sensitization, as measured by locomotor activity, and the over-expression of cocaine- and amphetamine-regulated transcript (CART) peptides after repeated administration of cocaine in mice. Repeated administrations of cocaine induced behavioral sensitization and CART over-expression in mice. The levels of striatal CART mRNA were significantly increased on the 3(rd) day. CART peptides were over-expressed on the 5(th) day in the striata of behaviorally sensitized mice. A higher proportion of CART(+) cells in the cocaine-treated mice were present in the nucleus accumbens (NAc) shell than in the dorsolateral (DL) part of caudate putamen (CP). The concomitant administration of both D1R and D2R antagonists, SCH 23390 (D1R selective) and raclopride (D2R selective), blocked cocaine induced-behavioral sensitization, CART over-expression, and cyclic adenosine 5'-monophosphate (cAMP)/protein kinase A (PKA)/phospho-cAMP response element-binding protein (pCREB) signal pathways. SCH 23390 more predominantly inhibited the locomotor activity, CART over-expression, pCREB and PKA activity than raclopride. Cocaine induced-behavioral sensitization was also attenuated in the both D1R and D2R knockout (KO) mice, respectively. CART over-expression and activated cAMP/PKA/pCREB signal pathways were inhibited in the D1R-KO mice, but not in the D2R-KO mice. It is suggested that behavioral sensitization, CART over-expression and activated cAMP/PKA/pCREB signal pathways induced by repeated administration of cocaine could be more predominantly mediated by D1R.
Volume 19(2)
Pages 89-97
Published 2015-3-1
DOI 10.4196/kjpp.2015.19.2.89
PMID 25729269
PMC PMC4342741
IF 1.805
Times Cited 11
Mice RBRC01080