Differential effects of blockade of dopamine D1-family receptors in nucleus Accumbens core or shell on reinstatement of heroin seeking induced by contextual and discrete cues
Differential effects of blockade of dopamine D1-family receptors in nucleus Accumbens core or shell on reinstatement of heroin seeking induced by contextual and discrete cues
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DOI：
10.1523/jneurosci.3926-07.2007
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发表时间：
2007-11-14
影响因子：
5.3
通讯作者：
Shaham, Yavin
中科院分区：
文献类型：
--
作者：
Bossert, Jennifer M.;Poles, Gabriela C.;Shaham, Yavin
在人类中，暴露于先前与海洛因摄入有关的环境环境可引起药物复发，但介导这种复发的神经元机制尚不清楚。使用药物复发模型，我们先前发现，在不同环境中药物强化反应消失后，将大鼠重新暴露于与海洛因相关的环境中，会恢复海洛因寻求。这种作用通过抑制谷氨酸在腹侧被盖区和内侧伏隔壳（中脑边缘多巴胺系统的组成部分）的传递而减弱。在这里，我们通过使用d -1家族受体拮抗剂SCH 23390 [R(+)-7-氯-8-羟基-3-甲基-1-苯基-2,3,4,5-四氢- 1h -3-苯氮平盐酸]，探索伏隔脑多巴胺在情境诱导的恢复中的作用。训练大鼠自我给药12 d；药物输注与一个离散的音调光提示配对。随后，在不同于药物自我给药背景的视觉、听觉、触觉和昼夜节律线索中，存在离散线索的情况下，海洛因增强的杠杆按压被熄灭。在原始的自我给药情境下，伏隔壳区全身和内侧或外侧注射SCH 23390可减弱情境诱导的海洛因寻求恢复，而伏隔核区注射SCH 23390则无效。相比之下，在没有该提示的杠杆按压消失后，在非药物环境下，核心而非外侧或内侧壳注射SCH 23390可减弱离散提示诱导的恢复。结果表明，伏隔核内侧和外侧壳d -1家族多巴胺受体的激活介导了情境诱导的海洛因寻求恢复，并首次证明了外侧壳多巴胺在条件性药物效应中的作用。结果还表明伏隔核和壳在情境与离散线索诱导的海洛因寻求恢复中具有新的可解离作用。
In humans, exposure to environmental contexts previously associated with heroin intake can provoke drug relapse, but the neuronal mechanisms mediating this relapse are unknown. Using a drug relapse model, we found previously that reexposing rats to heroin-associated contexts, after extinction of drug-reinforced responding in different contexts, reinstates heroin seeking. This effect is attenuated by inhibition of glutamate transmission in the ventral tegmental area and medial accumbens shell, components of the mesolimbic dopamine system. Here, we explored the role of dopamine of the accumbens in context-induced reinstatement by using the D-1-family receptor antagonist SCH 23390 [R(+)-7-chloro-8-hydroxy-3-methyl-1-phenyl-2,3,4,5-tetrahydro-1H-3-benzazepine hydrochloride]. Rats were trained to self-administer heroin for 12 d; drug infusions were paired with a discrete tone-light cue. Subsequently, the heroin-reinforced lever pressing was extinguished in the presence of the discrete cue in a context that differed from the drug self-administration context in terms of visual, auditory, tactile, and circadian cues. When tested in the original drug self-administration context, systemic and medial or lateral accumbens shell SCH 23390 injections attenuated context-induced reinstatement of heroin seeking, whereas accumbens core SCH 23390 injections were ineffective. In contrast, core but not lateral or medial shell SCH 23390 injections attenuated discrete-cue-induced reinstatement in a nondrug context after extinction of lever presses without this cue. Results indicate that activation of medial and lateral accumbens shell D-1-family dopamine receptors mediate context-induced reinstatement of heroin seeking and provide the first demonstration for a role of lateral shell dopamine in conditioned drug effects. Results also demonstrate novel dissociable roles of accumbens core and shell in context-versus discrete-cue-induced reinstatement of heroin seeking.