Atkins Alison L, Mashhoon Yasmin, Kantak Kathleen M
Department of Psychology, Boston University, Boston, MA 02215, United States.
Pharmacol Biochem Behav. 2008 Sep;90(3):481-91. doi: 10.1016/j.pbb.2008.04.007. Epub 2008 Apr 15.
Associations between cocaine and cues facilitate development and maintenance of addiction. We hypothesized that the ventral hippocampus is important for acquisition of these associations. Rats were trained to self-administer cocaine, with or without pre-exposure to distinct sets of cocaine- and saline-paired contextual cues. Next, rats were conditioned for 3 days with the distinct sets of contextual cues paired with cocaine and saline along with distinct discrete cues. Vehicle or lidocaine was infused into the ventral hippocampus prior to conditioning sessions. Following extinction, reinstatement of cocaine-seeking behavior was examined following exposure to contextual cues, discrete cues, or their combination. Inactivation of the ventral hippocampus during conditioning blocked acquisition of the association between cocaine and cocaine-paired contextual cues in that only lidocaine-treated rats with short-term cue exposure failed to reinstate responding in the presence of cocaine-paired contextual cues. Lidocaine also prevented rats in both cue exposure groups from discriminating between cocaine- and saline-paired contextual cues during reinstatement tests. Reinstatement induced by cocaine-paired discrete cues or by contextual and discrete cues together was not impaired for either cue exposure condition. The hippocampus is important for acquisition of the association between cocaine and context and in maintaining discrimination between cocaine-relevant and -irrelevant contextual cues.
可卡因与线索之间的关联促进成瘾的发展和维持。我们假设腹侧海马体对于习得这些关联很重要。对大鼠进行训练使其自我给药可卡因，训练过程中大鼠会接触或不接触与可卡因和生理盐水配对的不同情境线索组。接下来，让大鼠连续3天接受与可卡因和生理盐水配对的不同情境线索组以及不同离散线索的条件作用。在条件作用训练前，将溶剂或利多卡因注入腹侧海马体。消退训练后，在大鼠接触情境线索、离散线索或它们的组合后，检测可卡因觅求行为的恢复情况。条件作用训练期间腹侧海马体失活会阻碍可卡因与可卡因配对情境线索之间关联的习得，因为只有短期接触线索且接受利多卡因处理的大鼠在出现可卡因配对情境线索时未能恢复反应。利多卡因还阻止了两个线索接触组的大鼠在恢复测试中区分可卡因和生理盐水配对的情境线索。对于任何一种线索接触条件，由可卡因配对离散线索或由情境和离散线索共同诱导的恢复均未受损。海马体对于习得可卡因与情境之间的关联以及维持对与可卡因相关和不相关情境线索的区分很重要。
