Ghitza Udi E, Fabbricatore Anthony T, Prokopenko Volodymyr, Pawlak Anthony P, West Mark O
Department of Psychology, Rutgers University, Piscataway, New Jersey 08854, USA.
J Neurosci. 2003 Aug 13;23(19):7239-45. doi: 10.1523/JNEUROSCI.23-19-07239.2003.
Persistent neural processing of information regarding drug-predictive environmental stimuli may be involved in motivating drug abusers to engage in drug seeking after abstinence. The addictive effects of various drugs depend on the mesocorticolimbic dopamine system innervating the nucleus accumbens. We used single-unit recording in rats to test whether accumbens neurons exhibit responses to a discriminative stimulus (SD) tone previously paired with cocaine availability during cocaine self-administration. Presentation of the tone after 3-4 weeks of abstinence resulted in a cue-induced relapse of drug seeking under extinction conditions. Accumbens neurons did not exhibit tone-evoked activity before cocaine self-administration training but exhibited significant SD tone-evoked activity during extinction. Under extinction conditions, shell neurons exhibited significantly greater activity evoked by the SD tone than that evoked by a neutral tone (i.e., never paired with reinforcement). In contrast, core neurons responded indiscriminately to presentations of the SD tone or the neutral tone. Accumbens shell neurons exhibited significantly greater SD tone-evoked activity than did accumbens core neurons. Although the onset of SD tone-evoked activity occurred well before the earliest movements commenced (150 msec), this activity often persisted beyond the onset of tone-evoked movements. These results indicate that accumbens shell neurons exhibit persistent processing of information regarding reward-related stimuli after prolonged drug abstinence. Moreover, the accumbens shell appears to be involved in discriminating the motivational value of reward-related associative stimuli, whereas the accumbens core does not.
对与药物预测性环境刺激相关信息的持续神经处理，可能促使药物滥用者在戒断后仍进行觅药行为。各种药物的成瘾作用取决于支配伏隔核的中脑皮质边缘多巴胺系统。我们采用大鼠单神经元记录技术，来测试伏隔核神经元是否对在可卡因自我给药期间曾与可卡因可得性配对的辨别性刺激（SD）音调产生反应。在戒断3至4周后呈现该音调，会在消退条件下引发线索诱导的觅药复吸。在可卡因自我给药训练前，伏隔核神经元未表现出音调诱发的活动，但在消退期间表现出显著的SD音调诱发活动。在消退条件下，壳区神经元由SD音调诱发的活动显著大于由中性音调（即从未与强化配对）诱发的活动。相比之下，核心区神经元对SD音调或中性音调的呈现无差别反应。伏隔核壳区神经元比核心区神经元表现出显著更强的SD音调诱发活动。尽管SD音调诱发活动的起始远早于最早的动作开始（150毫秒），但该活动常常持续至音调诱发动作开始之后。这些结果表明，在长期药物戒断后，伏隔核壳区神经元对与奖赏相关刺激的信息进行持续处理。此外，伏隔核壳区似乎参与辨别与奖赏相关的联想性刺激的动机价值，而伏隔核核心区则不然。
