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Drug Addiction and Abuse

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

Chronic cocaine exposure changes inhibitory synaptic transmission in cholinergic neurons of laterodorsal tegmental nucleus

  • P2-344
  • 田岡 直史 / Naofumi Taoka:1 黒澤 諒 / Ryo Kurosawa: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 

Stress-induced reinstatement of cocaine-seeking is associated with an enhanced noradrenaline (NA) release and dopamine (DA) transmissions in the mesocorticolimbic circuit. The laterodorsal tegmental nucleus (LDT) is a major source of cholinergic input to the ventral tegmental area (VTA) and important for regulating DA neuronal activity. Because the LDT receives NA inputs from the locus coeruleus, we postulated that the LDT is involved in the stress-induced reinstatement of cocaine-seeking through activation of NA receptors. As a first step to address this possibility, we examined effects of NA on membrane potentials and synaptic transmissions of LDT cholinergic neurons in slice preparations that were obtained from 5-day cocaine- or saline-administered rats. Bath application of NA induced hyperpolarization and reduced EPSC amplitudes in both cocaine- and saline-treated neurons. On the other hand, NA remarkably attenuated IPSC amplitudes in cocaine- but not saline-treated neurons. This attenuation was mediated by α2 adrenoceptors because yohimbine but not prazosin or propranolol blocked the effect of NA. The NA-induced attenuation of IPSC amplitudes was still observed in the presence of strychnine, indicating that the modulation of GABAergic transmission was modulated by NA. Additionally, NA increased paired pulse ratios of GABAergic IPSCs and decreased frequencies of GABAergic mIPSCs without affecting their amplitudes, exhibiting that the NA effect was exerted by a presynaptic mechanism. These results suggest that chronic cocaine exposure induces plastic changes, in which inhibitory synaptic transmission in LDT cholinergic neurons becomes susceptible to NA. This plasticity might enhance LDT cholinergic neuronal activity in cocaine-experienced animals, contributing to the stress-induced reinstatement of cocaine-seeking via facilitating VTA DA neuronal activity.

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