Effects of cholinergic muscarinic receptor antagonists on the rewarding properties of methamphetamine and cocaine.

1999 Fiscal Year Final Research Report Summary

• Project/Area Number: 10672166
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: 応用薬理学・医療系薬学
• Research Institution: Kawasaki Medical School
• Principal Investigator: SHIMOSATO Kazuaki Faculty of Medicine, Kawasaki Medical School, Assistant, 医学部, 助手 (60154316)
• Co-Investigator(Kenkyū-buntansha): KITAYAMA Shigeo School of Dentistry, Hiroshima University, Assistant Professor, 歯学部, 助教授 (80177873)
• Project Period (FY): 1998 – 1999
• Keywords: methaphetamine / cocaine / reward / trihexyphenidyl / dopamine transporter / VMAT / ドーパミントランスポーター / ベシクルモノアミントランスポーター

Research Abstract

Previous in vitro studies with COS cells expressing rat dopamine (DA) transporter have proposed a possibility that a muscarinic receptor antagonist trihexyphenidyl (THP) may attenuate rewarding properties of cocaine. To address this possibility, we studied effects of THP and other muscarinic receptor antagonists benztropine (BNZ) and scopolamine (SCP) on conditioned place preference (CPP) induced by cocaine and methamphetamine (MAP) in mice. This behavioral study unexpectedly revealed that THP suppressed CPP induced by MAP, but not by cocaine. Neither BNZ nor SCP affected the rewarding property of MAP and cocaine. Subsequent in vivo microdialysis study examined the effect of THP on extracellular DA levels in the nucleus accumbens after injection of MAP in mice. MAP increased the DA levels during an initial 3 hr after injection. Treatment with THP antagonized the increase in DA levels produced by MAP. Furthermore, we investigated the effect of THP on DA release from vesicles of PC 12 cells. THP suppressed the MAP-induced increase of DA release from the vesicles of PC 12 cells. Taken together, these results indicate that THP may attenuate rewarding properties of MAP via, at lease in part, suppression of DA release from vesicular monoamine transporter (VMAT) into the cytoplasm of the presynaptic terminals.

Research Products

• [Publications] Shimosato K: "Simultaneous monitoring of conditioned place preference and locomotor sensitization following repeated administration of cocaine and metham phetamine"Pharmacology, Biochemistry and Behavior. (in press). (2000)
  • Description: 「研究成果報告書概要(和文)」より
• [Publications] Shimosato, K: "Simultaneous monitoring of conditioned place preference and locomotor sensitization following repeated administration of cocaine and methamphetamine"Pharmacologym Biochemistry and Behavior. (in press).
  • Description: 「研究成果報告書概要(欧文)」より