Funk D, Harding S, Juzytsch W, Lê A D
Department of Neurosciences, Center for Addiction and Mental Health (CAMH), 33 Russell St., Toronto, Ontario, Canada M5S 2S1.
Psychopharmacology (Berl). 2005 Dec;183(3):341-9. doi: 10.1007/s00213-005-0194-1. Epub 2005 Oct 27.
We and others have shown that a stressor commonly used in laboratory studies, intermittent footshock, reinstates alcohol seeking in a rat relapse model. The effects of more ethologically relevant stressors on reinstatement have not been examined. Here, we characterized the effects of social defeat (a naturalistic stressor) or a cue associated with the defeat experience on reinstatement of alcohol seeking. We also examined the effect of unconditioned and conditioned social defeat on alcohol self-administration.
Rats were trained to self-administer alcohol (12% w/v, 1 h day(-1)), and after stable responding, one group of animals received five exposures to social defeat paired with peppermint odor prior to daily self-administration sessions. After three more self-administration sessions, these rats were tested for the effects of the peppermint odor cue on self-administration. In another group of rats, the effects of three daily exposures to social defeat paired with peppermint odor on extinction of responding were examined. After further extinction sessions, the effect of the odor cue on reinstatement was tested in these animals. The acute effect of social defeat on reinstatement was examined in another group of animals.
Acute exposure to social defeat decreased alcohol self-administration, reduced rates of responding during extinction, and did not reinstate alcohol seeking. Exposure to a discrete odor cue previously paired with social defeat decreased alcohol self-administration but induced modest reinstatement of alcohol seeking.
Results provide the first demonstration of reinstatement of alcohol seeking by a cue paired with social defeat and are also in agreement with previous findings on the suppressive effect of social defeat stress on alcohol self-administration.
我们及其他研究人员已表明,实验室研究中常用的一种应激源——间歇性足部电击,会在大鼠复发模型中恢复对酒精的觅求行为。尚未研究更符合行为学的应激源对复吸的影响。在此,我们描述了社会挫败(一种自然主义应激源)或与挫败经历相关的线索对酒精觅求行为恢复的影响。我们还研究了无条件和有条件社会挫败对酒精自我给药的影响。
训练大鼠自我给药酒精(12% w/v,每天1小时),在稳定反应后,一组动物在每日自我给药前接受五次与薄荷气味配对的社会挫败暴露。在又进行三次自我给药后,测试这些大鼠薄荷气味线索对自我给药的影响。在另一组大鼠中,研究每日三次与薄荷气味配对的社会挫败暴露对反应消退的影响。在进一步的消退实验后,测试这些动物中气味线索对复吸的影响。在另一组动物中研究社会挫败对复吸的急性影响。
急性暴露于社会挫败会减少酒精自我给药,降低消退期间的反应率,且不会恢复酒精觅求行为。暴露于先前与社会挫败配对的离散气味线索会减少酒精自我给药,但会适度诱导酒精觅求行为的恢复。
结果首次证明了与社会挫败配对的线索会恢复酒精觅求行为,也与先前关于社会挫败应激对酒精自我给药抑制作用的研究结果一致。