Buffalari Deanne M, Feltenstein Matthew W, See Ronald E
Department of Neuroscience, University of Pittsburgh, A210 Langley Hall, Pittsburgh, PA, 15260, USA,
Psychopharmacology (Berl). 2013 Nov;230(2):319-27. doi: 10.1007/s00213-013-3156-z. Epub 2013 Jun 18.
Cue exposure therapy, which attempts to limit relapse by reducing reactivity to cocaine-paired cues through repeated exposures, has had limited success.
The current experiments examined cocaine cue-induced anxiogenesis and investigated whether a model of cue exposure therapy would reduce reinstatement of cocaine seeking in rats with a history of cocaine self-administration.
Male rats experienced daily intravenous cocaine self-administration. Rats then experienced exposure to either the self-administration context or the context plus noncontingent presentations of cocaine-paired cues. Immediately following exposure, anxiety-like behavior was measured using elevated plus maze and defensive burying tests. In a second group of rats, self-administration was followed by 7 days of exposure to the context, context + noncontingent cue exposure, lever extinction, or cue + lever extinction. All animals then underwent two contingent cue-induced reinstatement tests separated by 7 days of lever extinction.
Exposure to noncontingent cocaine-paired cues in the self-administration context increased anxiety-like behavior on the defensive burying test. Animals that experienced lever + cue extinction displayed the least cocaine seeking on the first reinstatement test, and lever extinction reduced cocaine seeking below context exposure or context + noncontingent cue exposure. All animals had similar levels of cocaine seeking on the second reinstatement test.
Noncontingent cue exposure causes anxiety, and noncontingent cue and context exposure are less effective at reducing contingent cue-induced reinstatement than lever or lever + cue extinction. These data indicate that active extinction of the drug-taking response may be critical for reduction of relapse proclivity in former cocaine users.
线索暴露疗法试图通过反复暴露来降低对与可卡因相关线索的反应性,从而限制复吸,但成效有限。
当前实验研究了可卡因线索诱发的焦虑症,并探究线索暴露疗法模型是否能减少有可卡因自我给药史的大鼠的可卡因觅求行为复燃。
雄性大鼠每日进行静脉注射可卡因自我给药。然后,大鼠分别经历自我给药环境或该环境加上与可卡因相关线索的非偶然性呈现。暴露后,立即使用高架十字迷宫和防御性埋土试验测量类似焦虑的行为。在另一组大鼠中,自我给药后,进行为期7天的环境暴露、环境+非偶然性线索暴露、杠杆消退或线索+杠杆消退。然后,所有动物接受两次由7天杠杆消退隔开的偶然性线索诱发的复燃试验。
在自我给药环境中暴露于与可卡因相关的非偶然性线索会增加防御性埋土试验中类似焦虑的行为。经历杠杆+线索消退的动物在首次复燃试验中表现出最少的可卡因觅求行为,并且杠杆消退使可卡因觅求行为低于环境暴露或环境+非偶然性线索暴露。在第二次复燃试验中,所有动物的可卡因觅求水平相似。
非偶然性线索暴露会引发焦虑,并且非偶然性线索和环境暴露在减少偶然性线索诱发的复燃方面不如杠杆或杠杆+线索消退有效。这些数据表明,主动消除药物摄取反应可能对降低既往可卡因使用者的复吸倾向至关重要。