Predominant D1 Receptors Involvement in the Over-expression of CART Peptides after Repeated Cocaine Administration

• 영문명: Predominant D₁ Receptors Involvement in the Over-expression of CART Peptides after Repeated Cocaine Administration
• 발행기관: 대한생리학회-대한약리학회
• 저자명: Zhenzhen Hu Eun-Hye Oh Yeon Bok Chung Jin Tae Hong Ki-Wan Oh
• 간행물 정보: 『The Korean Journal of Physiology & Pharmacology』제19권 제2호, 89~97쪽, 전체 9쪽
• 주제분류: 의약학 > 의학일반
• 파일형태: PDF
• 발행일자: 2015.01.01

영문 초록

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.

키워드

cAMP cAMP/PKA/pCREB signal pathways CART Cocaine Dopamine receptors