Nicolas Celine, Russell Trinity I, Shaham Yavin, Ikemoto Satoshi
Behavioral Neuroscience Branch, Intramural Research Program, National Institute on Drug Abuse, Baltimore, MD, United States.
Front Neurosci. 2022 Feb 7;15:824741. doi: 10.3389/fnins.2021.824741. eCollection 2021.
Studies using either continuous or intermittent access cocaine self-administration procedures showed that cocaine seeking increases during abstinence (incubation of cocaine craving), and that this effect is higher after intermittent cocaine access. Other studies showed that cocaine abstinence is characterized by the emergence of stress- and anxiety-related states which were hypothesized to increase relapse vulnerability. We examined whether incubation of cocaine craving and anxiety-related behaviors are correlated and whether intermittent cocaine self-administration would potentiate these behaviors during abstinence. Male rats self-administered cocaine either continuously (6 h/day) or intermittently (5 min ON, 25 min OFF × 12) for 14 days, followed by relapse tests after 1 or 21 abstinence days. A group of rats that self-administered saline served as a control. Anxiety-related behaviors were measured on the same abstinence days, using the novelty induced-hypophagia test. Finally, motivation for cocaine was measured using a progressive ratio reinforcement schedule. Lever-presses after 21 abstinence days were higher than after 1 day and this incubation effect was higher in the intermittent access group. Progressive ratio responding was also higher after intermittent cocaine access. Intermittent and continuous cocaine access did not induce anxiety-like responses in the novelty-induced hypophagia test after 1 or 21 abstinence days. Independent of the access condition, incubation of cocaine seeking was not correlated with the novelty-induced hypophagia measures. Results suggest that cocaine-induced anxiety-related states during protracted abstinence do not contribute to incubation of cocaine craving. However, this conclusion is tentative because we used a single anxiety-related measure and did not test female rats.
使用连续或间歇性获取可卡因自我给药程序的研究表明，在禁欲期间对可卡因的寻觅会增加（可卡因渴望的潜伏期），并且这种效应在间歇性获取可卡因后更高。其他研究表明，可卡因禁欲的特征是出现与压力和焦虑相关的状态，据推测这些状态会增加复发易感性。我们研究了可卡因渴望的潜伏期与焦虑相关行为是否相关，以及间歇性可卡因自我给药是否会在禁欲期间增强这些行为。雄性大鼠连续（每天6小时）或间歇性（开5分钟，关25分钟×12次）自我给药可卡因14天，然后在禁欲1天或21天后进行复发测试。一组自我给药生理盐水的大鼠作为对照。在相同的禁欲日，使用新奇诱导性摄食减少试验测量焦虑相关行为。最后，使用渐进比率强化程序测量对可卡因的动机。禁欲21天后的杠杆按压次数高于禁欲1天后，并且这种潜伏期效应在间歇性获取组中更高。间歇性获取可卡因后，渐进比率反应也更高。在禁欲1天或21天后的新奇诱导性摄食减少试验中，间歇性和连续获取可卡因均未诱发类似焦虑的反应。与获取条件无关，对可卡因寻觅的潜伏期与新奇诱导性摄食减少测量值不相关。结果表明，长期禁欲期间可卡因诱发的与焦虑相关的状态不会导致可卡因渴望的潜伏期增加。然而，这一结论是初步的，因为我们使用了单一的与焦虑相关的测量方法，并且没有测试雌性大鼠。
