Xie Xiaohu, Wells Audrey M, Fuchs Rita A
Department of Chemistry,North Carolina State University,Raleigh,USA.
Behavioural Genetics Laboratory, Department of Psychiatry,Harvard Medical School, McLean Hospital,Belmont,USA.
Int J Neuropsychopharmacol. 2014 Sep;17(9):1533-8. doi: 10.1017/S1461145714000340. Epub 2014 Mar 21.
Despite the well-documented involvement of dopamine D1-like receptor stimulation in cocaine-induced goal-directed behaviours, little is known about the specific contribution of D1-like receptor populations in the dorsal hippocampus (DH) to drug context-induced cocaine-seeking or drug-reinforced instrumental behaviours. To investigate this question, rats were trained to lever press for un-signalled cocaine infusions in a distinct context followed by extinction training in a different context. Cocaine-seeking behaviour (non-reinforced lever responding) was then assessed in the previously cocaine-paired and extinction contexts. SCH23390-induced D1-like receptor antagonism in the DH, but not the overlying trunk region of the somatosensory cortex, dose-dependently inhibited drug context-induced cocaine-seeking behaviour, without altering cocaine-reinforced instrumental responding, cocaine intake, food-reinforced instrumental responding, or general motor activity, relative to vehicle treatment. These findings suggest that D1-like receptor stimulation in the DH is critical for the incentive motivational effects and/or memory of cocaine-paired contextual stimuli that contribute to drug-seeking behaviour.
尽管多巴胺D1样受体刺激在可卡因诱导的目标导向行为中的作用已有充分记录,但对于背侧海马体(DH)中D1样受体群体对药物情境诱导的可卡因寻求或药物强化工具性 行为的具体贡献知之甚少。为了研究这个问题,训练大鼠在不同情境下按压杠杆以获得无信号的可卡因注射,随后在不同情境下进行消退训练。然后在先前与可卡因配对的情境和消退情境中评估可卡因寻求行为(非强化杠杆反应)。相对于载体处理,SCH23390诱导的DH而非体感皮层的覆盖躯干区域中的D1样受体拮抗作用剂量依赖性地抑制了药物情境诱导的可卡因寻求行为,而不改变可卡因强化的工具性反应、可卡因摄入量、食物强化的工具性反应或一般运动活动。这些发现表明,DH中的D1样受体刺激对于促成药物寻求行为的可卡因配对情境刺激的激励动机效应和/或记忆至关重要。