Hurd Y L, McGregor A, Pontén M
Karolinska Institute, Department of Clinical Neuroscience, Stockholm, Sweden.
Eur J Neurosci. 1997 Dec;9(12):2541-8. doi: 10.1111/j.1460-9568.1997.tb01683.x.
Nucleus accumbens dopamine is often hypothesized as the critical factor for modulating cocaine self-administration. In the current study we examined the extent to which dopamine in the amygdala could contribute to cocaine intake behaviour and modify nucleus accumbens dopamine levels. Rats were trained to self-administer intravenous cocaine (1.5 mg/kg/injection) under a fixed-ratio reinforcement schedule in daily 3 h operant training sessions. In the first in vivo microdialysis experiment, extracellular dopamine levels were found to be increased 200% of baseline in the amygdala and by 400% in the nucleus accumbens. Although cocaine induced similar profiles of dopamine overflow in the two mesolimbic areas, in the nucleus accumbens the latency of the dopaminergic response was shorter (three- to four-fold) during both initiation and termination of the cocaine self-administration session than in the amygdala. Despite achieving a stable self-regulated pattern of cocaine intake and high dopamine concentrations in the nucleus accumbens, a unilateral injection of the D1 receptor antagonist SCH 23390 (0.5 or 1.5 microg) into the amygdala was still able to increase the rate of cocaine intake. This behavioural effect was accompanied by a dose-dependent increase in nucleus accumbens dopamine levels; at the highest SCH 23390 concentration cocaine intake was increased by 400% and dopamine levels were potentiated by an additional 400%. In vivo autoradiography using [3H]SCH 23390 showed that D1 receptor sites contributing to the behavioural and subsequent neurochemical effects were predominantly localized to the amygdala and not the nucleus accumbens. Altogether these results point to a significant contribution of in vivo amygdala D1 dopamine transmission to cocaine self-administration behaviour.
伏隔核多巴胺常被假定为调节可卡因自我给药的关键因素。在本研究中，我们考察了杏仁核中的多巴胺在多大程度上会影响可卡因摄取行为并改变伏隔核多巴胺水平。大鼠在每日3小时的操作性训练中，按照固定比率强化程序接受静脉注射可卡因（1.5毫克/千克/注射）的训练。在首个体内微透析实验中，发现杏仁核细胞外多巴胺水平比基线升高了200%，伏隔核则升高了400%。虽然可卡因在两个中脑边缘区域诱发了相似的多巴胺溢出情况，但在可卡因自我给药过程的起始和结束阶段，伏隔核中多巴胺能反应的潜伏期比杏仁核短（三到四倍）。尽管实现了稳定的可卡因摄取自我调节模式且伏隔核中有高浓度多巴胺，但向杏仁核单侧注射D1受体拮抗剂SCH 23390（0.5或1.5微克）仍能提高可卡因摄取率。这种行为效应伴随着伏隔核多巴胺水平的剂量依赖性增加；在最高SCH 23390浓度下，可卡因摄取增加了400%，多巴胺水平又额外增强了400%。使用[3H]SCH 23390进行的体内放射自显影显示，对行为和后续神经化学效应起作用的D1受体位点主要定位于杏仁核而非伏隔核。总之，这些结果表明体内杏仁核D1多巴胺传递对可卡因自我给药行为有显著贡献。
