Marchant Nathan J, Kaganovsky Konstantin
Behavioral Neuroscience Research Branch, Intramural Research Program, National Institute on Drug Abuse.
Behav Neurosci. 2015 Jun;129(3):281-91. doi: 10.1037/bne0000050. Epub 2015 Apr 27.
In humans, places or contexts previously associated with alcohol use often provoke relapse during abstinence. This phenomenon is modeled in laboratory animals using the ABA renewal procedure, in which extinction training in context (B) suppresses alcohol seeking, and renewal of this seeking occurs when the animal returns to the original training context (A). However, extinction training does not adequately capture the motivation for abstinence in human alcoholics who typically self-initiate abstinence in response to the negative consequences of excessive use. We recently developed a procedure to study renewal in laboratory rats after abstinence imposed by negative consequences (footshock punishment). The mechanisms of renewal of punished alcohol seeking are largely unknown. Here, we used the D1-family receptor antagonist SCH 23390 to examine the role of nucleus accumbens (NAc) shell and core dopamine in renewal of alcohol seeking after punishment-imposed abstinence. We trained alcohol-preferring "P rats" to self-administer 20% alcohol in Context A and subsequently suppressed alcohol taking via response-contingent footshock punishment in Context B. We tested the effects of systemic, NAc shell, or NAc core injections of SCH 23390 on renewal of alcohol seeking after punishment-imposed abstinence. We found that both systemic and NAc shell and core injections of SCH 23390 decreased renewal of punished alcohol seeking. Our results demonstrate a critical role of NAc dopamine in renewal of alcohol seeking after punishment-imposed abstinence. We discuss these results in reference to the brain mechanisms of renewal of alcohol seeking after extinction versus punishment.
在人类中，先前与饮酒相关的场所或情境往往会在戒酒期间引发复饮。这种现象在实验动物中通过ABA复现程序进行模拟，即在情境（B）中进行消退训练会抑制对酒精的觅求，而当动物回到原来的训练情境（A）时，这种觅求行为就会复现。然而，消退训练并不能充分体现人类酗酒者戒酒的动机，他们通常是因过度饮酒的负面后果而自行开始戒酒。我们最近开发了一种程序，用于研究在因负面后果（足部电击惩罚）导致戒酒的实验大鼠中的复现现象。惩罚后酒精觅求行为复现的机制在很大程度上尚不清楚。在此，我们使用D1家族受体拮抗剂SCH 23390来研究伏隔核（NAc）壳部和核心多巴胺在惩罚导致戒酒之后酒精觅求行为复现中的作用。我们训练偏好酒精的“P大鼠”在情境A中自行摄入20%的酒精，随后在情境B中通过基于反应的足部电击惩罚来抑制酒精摄入。我们测试了全身性、NAc壳部或NAc核心注射SCH 23390对惩罚导致戒酒之后酒精觅求行为复现的影响。我们发现，全身性、NAc壳部和核心注射SCH 23390均降低了惩罚后酒精觅求行为的复现。我们的结果证明了NAc多巴胺在惩罚导致戒酒之后酒精觅求行为复现中起关键作用。我们参照消退与惩罚后酒精觅求行为复现的脑机制来讨论这些结果。
