Response contingency directs long-term cocaine-induced neuroplasticity in prefrontal and striatal dopamine terminals

详细信息    查看全文

• 作者：Joost Wiskerke^a ; ¹ ; Anton N.M. Schoffelmeer^a ; Taco J. De Vries^a ; ^b ; ^{tj.devries@vumc.nl" class="auth_mail" title="E-mail the corresponding author}
• 关键词：Drug addiction ; Drug-induced plasticity ; Natural reward ; Psychostimulant ; Dopamine ; Response contingency
• 刊名：European Neuropsychopharmacology
• 出版年：2016
• 出版时间：October 2016
• 年：2016
• 卷：26
• 期：10
• 页码：1667-1672
• 全文大小：676 K

文摘

Exposure to addictive substances such as cocaine is well-known to alter brain organisation. Cocaine-induced neuroadaptations depend on several factors, including drug administration paradigm. To date, studies addressing the consequences of cocaine exposure on dopamine transmission have either not been designed to investigate the role of response contingency or focused only on short-term neuroplasticity. We demonstrate a key role of response contingency in directing long-term cocaine-induced neuroplasticity throughout projection areas of the mesocorticolimbic dopamine system. We found enhanced electrically-evoked [³H]dopamine release from superfused brain slices of nucleus accumbens shell and core, dorsal striatum and medial prefrontal cortex three weeks after cessation of cocaine self-administration. In yoked cocaine rats receiving the same amount of cocaine passively, sensitised dopamine terminal reactivity was only observed in the nucleus accumbens core. Control sucrose self-administration experiments demonstrated that the observed neuroadaptations were not the result of instrumental learning per se. Thus, long-term withdrawal from cocaine self-administration is associated with widespread sensitisation of dopamine terminals throughout frontostriatal circuitries.