Ethanol-associated olfactory stimuli reinstate ethanol-seeking behavior after extinction and modify extracellular dopamine levels in the nucleus accumbens
Ethanol-associated olfactory stimuli reinstate ethanol-seeking behavior after extinction and modify extracellular dopamine levels in the nucleus accumbens
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DOI：
10.1111/j.1530-0277.1999.tb04070.x
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发表时间：
1999-11-01
影响因子：
3.2
通讯作者：
Weiss, F
中科院分区：
文献类型：
--
作者：
Katner, SN;Weiss, F
背景：酒精渴望或由酒精相关线索引起的自动行为反应被认为有助于戒酒个体的复发风险。然而，迄今为止只有有限的直接实验证据支持这一假设。本研究采用操作性反应-恢复模型研究乙醇相关环境刺激对酒精寻求行为和伏隔核（NAcc）细胞外多巴胺（DA）水平的影响。方法：将雄性Wistar大鼠植入用于微透析的脑内引导管，并训练其在离散嗅觉鉴别刺激（S Delta’S）的存在下自主给药乙醇，这表明乙醇（10% w/v）的可用性与非奖励刺激（50 μ M奎宁盐酸溶液）的可用性。在辨别学习阶段之后，对乙醇（和奎宁）的反应通过扣留饮用溶液以及相应的S δ来消除。在达到并维持小于或等于5次反应/次的消退标准后，大鼠非偶然地暴露于乙醇和非奖励S δ，但没有乙醇或奎宁的可用性。结果：乙醇S δ S诱导反应恢复明显，非奖励Sh无明显作用。在出现S - Delta之前的20分钟“等待期”暴露于手术腔与透析液DA水平小幅但显著增加有关。随后暴露于乙醇S δ和恢复阶段的开始伴随着少量但显著的DA外排减少。暴露于无奖励的S δ并没有改变DA水平。结论：行为数据证实，乙醇预测性判别刺激在消失后可靠地诱发了酒精寻求行为。等待期DA外排的增加证实了先前的发现，并表明对获得乙醇的预期激活了中边缘DA神经元。在给予乙醇Sh的动物恢复过程开始后，DA外排的减少可能反映了与预测（即乙醇可用性）和实际（即没有乙醇）刺激事件之间不匹配相关的神经化学事件。这种可能性得到了无奖励S δ的大鼠的DA外排没有变化的支持，S δ是一个不涉及这种不匹配的测试条件。总的来说，这些发现为条件反射过程在酒精寻求行为控制中的作用提供了进一步的证据，并进一步支持了对药物相关刺激的条件反射可能是慢性酒精滥用和复发的重要因素的假设。
Background: Alcohol craving or automatic behavioral responses provoked by alcohol-related cues are thought to contribute to relapse risk in abstinent individuals. However, there is to date only limited direct experimental evidence that supports this hypothesis. The present study employed an operant response-reinstatement model to examine the effects of ethanol-associated environmental stimuli on alcohol-seeking behavior and extracellular dopamine (DA) levels in the nucleus accumbens (NAcc).Methods: Male Wistar rats were prepared with intracerebral guide cannulae for microdialysis and trained to operantly self-administer ethanol in the presence of discrete olfactory discriminative stimuli (S Delta's) signaling the availability of ethanol (10% w/v) versus a nonrewarding stimulus (a 50 mu M quinine HCl solution). After the discrimination learning phase, responding for ethanol (and quinine) was extinguished by withholding the drinking solutions as well as the corresponding S Delta's. After reaching and maintaining an extinction criterion of less than or equal to 5 responses/session, the rats were exposed noncontingently to the ethanol and nonreward S Delta's but without the availability of ethanol or quinine.Results: The ethanol S Delta's, but not nonreward Sh's, elicited significant recovery of responding. Exposure to the operant chamber during a 20 min "waiting period" before presentation of the S Delta's was associated with a small but significant increase in dialysate DA levels. Subsequent exposure to the ethanol S Delta and onset of the reinstatement session was accompanied by a small but significant decrease in DA efflux. Exposure to the nonreward S Delta did not alter DA levels.Conclusions: The behavioral data confirm that ethanol-predictive discriminative stimuli reliably elicit ethanol-seeking behavior after extinction. The increase in DA efflux during the waiting period confirms earlier findings and suggests that anticipation of access to ethanol activates mesolimbic DA neurons. The decrease in DA efflux after onset of the reinstatement session in animals that were presented with the ethanol Sh's may reflect neurochemical events associated with the mismatch between the predicted (i.e., ethanol availability) and actual (i.e., absence of ethanol) stimulus events. This possibility is supported by the lack of changes in DA efflux in rats that were presented with the nonreward S Delta's, a test condition that did not involve such a mismatch. Overall, the findings provide further evidence for a role of conditioning processes in the control of alcohol-seeking behavior and, by extension, support the hypothesis that conditioned responses to drug-related stimuli may be an important factor in chronic alcohol abuse and relapse.