Predominant D<sub>1</sub> Receptors Involvement in the Over-expression of CART Peptides after Repeated Cocaine Administration
Predominant D<sub>1</sub> Receptors Involvement in the Over-expression of CART Peptides after Repeated Cocaine Administration
- Zhenzhen Hu Eun-Hye Oh Yeon Bok Chung Jin Tae Hong Ki-Wan Oh
- 대한생리학회-대한약리학회
- The Korean Journal of Physiology & Pharmacology
- 제19권 제2호
- 등재여부 : KCI등재
- 2015.01
- 89 - 97 (9 pages)
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<sup>rd</sup> day. CART peptides were over-expressed on the 5<sup>th</sup> day in the striata of behaviorally sensitized mice. A higher proportion of CART<sup>+</sup> 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 D<sub>1</sub>R and D<sub>2</sub>R antagonists, SCH 23390 (D<sub>1</sub>R selective) and raclopride (D<sub>2</sub>R 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 (<i>p</i>CREB) signal pathways. SCH 23390 more predominantly inhibited the locomotor activity, CART over-expression, <i>p</i>CREB and PKA activity than raclopride. Cocaine induced-behavioral sensitization was also attenuated in the both D<sub>1</sub>R and D<sub>2</sub>R knockout (KO) mice, respectively. CART over-expression and activated cAMP/PKA/<i>p</i>CREB signal pathways were inhibited in the D<sub>1</sub>R-KO mice, but not in the D<sub>2</sub>R-KO mice. It is suggested that behavioral sensitization, CART over-expression and activated cAMP/PKA/<i>p</i>CREB signal pathways induced by repeated administration of cocaine could be more predominantly mediated by D<sub>1</sub>R.