Peoples Laura L, Lynch Kevin G, Lesnock Jamie, Gangadhar Nidhi
Department of Psychology, University of Pennsylvania, Philadelphia 19104, USA.
J Neurophysiol. 2004 Jan;91(1):314-23. doi: 10.1152/jn.00638.2003. Epub 2003 Oct 1.
During a chronic extracellular recording session, animals with a history of cocaine self-administration were allowed to initiate drug seeking under drug-free conditions. Later, in the same recording session, animals engaged in intravenous cocaine self-administration. During the drug-free period, 31% of 70 accumbal neurons showed a significant increase in average firing rate in association with either or both the exposure to cues that signaled the onset of cocaine availability and the subsequent onset of drug-seeking behavior. The neurons that showed an average excitatory response during the drug-free period were the only group of neurons that showed an average excitatory phasic response to cocaine-reinforced lever presses during the drug self-administration session. A majority of the neurons that were activated during the drug-free period, like the majority of other neurons, showed decreases in average firing in response to self-administered cocaine. However, the neurons that were activated during the drug-free period maintained a higher rate of firing throughout the self-administration session than did other accumbal neurons. The data of the present study are consistent with the conclusion that accumbal neurons contribute to, or otherwise process, initiation of drug seeking under drug-free conditions and that they do so via primarily excitatory responses. Furthermore, there is continuity between the drug-free and -exposed conditions in neural responses associated with drug seeking. Finally, the data have potential implications for understanding mechanisms that transduce accumbal-mediated drug effects that contribute to drug addiction.
在一次慢性细胞外记录实验中，有可卡因自我给药史的动物在无药条件下被允许开始寻求药物。之后，在同一次记录实验中，动物进行静脉注射可卡因自我给药。在无药期间，70个伏隔核神经元中有31%表现出平均放电率显著增加，这与暴露于预示可卡因可得性开始的线索以及随后的药物寻求行为的开始中的一个或两个有关。在无药期间表现出平均兴奋性反应的神经元是在药物自我给药实验期间对可卡因强化的杠杆按压表现出平均兴奋性相位反应的唯一一组神经元。在无药期间被激活的大多数神经元，与大多数其他神经元一样，在对自我给药的可卡因作出反应时平均放电减少。然而，在无药期间被激活的神经元在整个自我给药实验期间的放电率比其他伏隔核神经元更高。本研究的数据与以下结论一致：伏隔核神经元在无药条件下促成或参与药物寻求的启动，并且它们主要通过兴奋性反应来做到这一点。此外，在与药物寻求相关的神经反应中，无药和用药条件之间存在连续性。最后，这些数据对于理解转导伏隔核介导的导致药物成瘾的药物作用的机制具有潜在意义。
