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Drug Addiction and Abuse

開催日 2014/9/12
時間 11:00 - 12:00
会場 Poster / Exhibition(Event Hall B)

Cholinergic transmission to and dopaminergic transmission from the ventral tegmental area contribute to the expression of cocaine-conditioned place preference

  • P2-343
  • 篠原 史弥 / Fumiya Shinohara:1 南 雅文 / Masabumi Minami:1 金田 勝幸 / Katsuyuki Kaneda:1 
  • 1:北海道大院薬薬理 / Dept Pharmacol, Grad Sch Pharm Sci, Hokkaido Univ, Sapporo, Japan 

In drug addiction, drug-related memories, which are retrieved by drug-experienced environmental cues and contexts, induce craving and relapse. Thus, exploring the mechanisms for formation and retrieval of drug-related memories is important in developing clinically relevant therapies for drug addiction. We have previously reported that cholinergic transmission from the laterodorsal tegmental nucleus (LDT) to dopamine (DA) neurons in the ventral tegmental area (VTA) is involved in acquiring rewarding memories of cocaine. In the present study, we investigated whether cholinergic transmission in the VTA, VTA DA neuronal activity, and DA transmission in the mesocorticolimbic system are associated with cocaine-related memory retrieval using conditioned place preference (CPP) paradigm. Intra-VTA injection of a mixture of scopolamine and mecamylamine immediately before the posttest session significantly reduced the cocaine-induced CPP, indicating that cholinergic signaling in the VTA is necessary for the expression of CPP. Because cholinergic input to the VTA is considered to activate DA neurons, we next examined the effect of inactivation of VTA DA neuronal activity and found that intra-VTA injection of a mixture of baclofen and muscimol also significantly reduced the cocaine-induced CPP. Additionally, injection of a D1 receptor selective antagonist SCH23390 into the mPFC, one of the targets of VTA DA projections, significantly decreased the cocaine-induced CPP. Together, these findings suggest that cholinergic signal transmission from the LDT to the VTA and subsequent DA transmission from the VTA to the mPFC are critical for the retrieval of environmental context-dependent cocaine-related memory.

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