Inactivation of the bed nucleus of the stria terminalis in an animal model of relapse: effects on conditioned cue-induced reinstatement and its enhancement by yohimbine
Inactivation of the bed nucleus of the stria terminalis in an animal model of relapse: effects on conditioned cue-induced reinstatement and its enhancement by yohimbine
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DOI：
10.1007/s00213-010-2008-3
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发表时间：
2011-01-01
影响因子：
3.4
通讯作者：
See, Ronald E.
中科院分区：
文献类型：
--
作者：
Buffalari, Deanne M.;See, Ronald E.
与毒品有关的暗示和压力会增加戒断毒品使用者的渴望，并导致更大的复发风险。药物寻求的恢复的动物模型已被用于研究神经回路，通过该神经回路，药物相关的线索或压力暴露引起药物寻求。最近的证据表明，育亨宾压力对随后的线索诱发的恢复有很强的增强作用;然而，目前还没有研究这种相互作用的神经基础。目前的研究检查了终纹床核（BNST）的失活是否会影响条件线索引起的可卡因寻求的恢复，雄性大鼠经历每日IV可卡因自我给药，随后在没有可卡因配对线索的情况下杠杆反应消失。在可卡因配对线索的呈现过程中，测量反应的恢复，与药理学应激，育亨宾（2.5毫克/公斤，IP），或线索和育亨宾的组合预处理后，所有三种条件下导致可卡因寻求的恢复，与最高的反应后看到的线索和育亨宾的组合。可逆失活的BNST使用的γ-氨基丁酸受体激动剂，巴氯芬+蝇蕈醇，显着减少所有三种形式的reinstatment.These结果表明，可卡因寻求可卡因配对线索引起的BNST的作用，并建议BNST作为一个关键的调解人的相互作用的压力和线索恢复可卡因寻求。
Drug-associated cues and stress increase craving and lead to greater risk of relapse in abstinent drug users. Animal models of reinstatement of drug seeking have been utilized to study the neural circuitry by which either drug-associated cues or stress exposure elicit drug seeking. Recent evidence has shown a strong enhancing effect of yohimbine stress on subsequent cue-elicited reinstatement; however, there has been no examination of the neural substrates of this interactive effect.The current study examined whether inactivation of the bed nucleus of the stria terminalis (BNST), an area previously implicated in stress activation of drug seeking, would affect reinstatement of cocaine seeking caused by conditioned cues, yohimbine stress, or the combination of these factors.Male rats experienced daily IV cocaine self-administration, followed by extinction of lever responding in the absence of cocaine-paired cues. Reinstatement of responding was measured during presentation of cocaine-paired cues, following pretreatment with the pharmacological stressor, yohimbine (2.5 mg/kg, IP), or the combination of cues and yohimbine.All three conditions led to reinstatement of cocaine seeking, with the highest responding seen after the combination of cues and yohimbine. Reversible inactivation of the BNST using the gamma-aminobutyric acid receptor agonists, baclofen + muscimol, significantly reduced all three forms of reinstatement.These results demonstrate a role for the BNST in cocaine seeking elicited by cocaine-paired cues, and suggest the BNST as a key mediator for the interaction of stress and cues for the reinstatement of cocaine seeking.