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演題詳細

Poster

薬物依存、乱用
Drug Addiction and Abuse

開催日 2014/9/12
時間 14:00 - 15:00
会場 Poster / Exhibition(Event Hall B)

コカイン慢性投与による背外側被蓋核コリン作動性ニューロンでの膜特性可塑性の誘導
Intrinsic membrane plasticity induced after chronic cocaine administration in the laterodorsal tegmental nucleus cholinergic neurons

  • P2-342
  • 金田 勝幸 / Katsuyuki Kaneda:1 黒澤 諒 / Ryo Kurosawa:1 田岡 直史 / Naofumi Taoka:1 南 雅文 / Masabumi Minami:1 
  • 1:北海道大院・薬・薬理 / Dept Pharmacol, Grad Sch Pharm Sci, Hokkaido Univ, Sapporo, Japan 

The laterodorsal tegmental nucleus (LDT) contains cholinergic neurons, which project to dopamine (DA) neurons in the ventral tegmental area (VTA) and modulate their activity. We have recently reported that repeated cocaine exposure induces presynaptic plasticity in glutamatergic synaptic transmission in LDT cholinergic neurons, implicating that the increased LDT cholinergic activity is associated with cocaine addiction. To further investigate the involvement of LDT cholinergic neurons in cocaine addiction, here we examined whether the intrinsic membrane plasticity of cholinergic neurons is induced by repeated cocaine exposure. Whole-cell current clamp recordings performed in LDT cholinergic neurons in slice preparations, which were prepared from 5-day cocaine- or saline-injected rats, revealed that the number of spikes induced by depolarizing current injections in cocaine-treated neurons was significantly larger than that in saline-treated neurons. Bath application of TEA, 4-AP, or apamin reduced or increased, respectively, the number of spikes both in cocaine- and saline-treated neurons, whereas the differences in the number of spikes after the applications of the blockers between cocaine- and saline-treated neurons were still significant. On the other hand, riluzole application reduced the spike numbers in both cocaine- and saline-treated neurons and the difference in the number of spikes before riluzole application between the two groups disappeared after the drug application. Additionally, voltage-clamp recordings revealed that the magnitude of riluzole-sensitive current density in cocaine-treated neurons was significantly larger than that in saline-treated neurons. These results suggest that chronic cocaine exposure increases cholinergic neuronal excitability via enhancing persistent sodium channel currents in the LDT and imply that enhanced cholinergic neuronal activity may contribute to the development of cocaine addiction.

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