Increased heroin intake and relapse vulnerability in intermittent relative to continuous self-administration: Sex differences in rats.
Increased heroin intake and relapse vulnerability in intermittent relative to continuous self-administration: Sex differences in rats.
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DOI：
10.1111/bph.15791
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发表时间：
2023-04
影响因子：
7.3
通讯作者：
中科院分区：
文献类型：
--
作者：
使用间歇性获取药物自我给药的研究表明，与持续获取相比，服用和寻求可卡因和芬太尼的动机更强。在这项研究中，我们研究了在强迫或自愿戒断后，雄性和雌性大鼠间歇性和连续自我给药对海洛因摄入量、自我给药模式和线索诱导的海洛因寻求的影响。我们还模拟了海洛因及其活性代谢物的大脑水平。将大鼠训练成连续（6小时/天；10天）或间歇（6小时/天；5分钟进入/30分钟；10天）先给药，然后给药海洛因（0.075 mg/kg/inf）。海洛因及其代谢物的脑水平用药代动力学软件建模。接下来，在戒断1天或21天后评估海洛因寻求。在两次试验之间，大鼠被强迫或自愿戒酒。使用阴道涂片试验测量发情周期。间歇性获取加剧了海洛因的自我给药，其特征是突发性摄入，产生更高的海洛因和6-单乙酰吗啡浓度的脑峰值。此外，间歇性接触增加了线索诱导的海洛因寻求在早期戒断期间，而不是后期。在间歇性接触海洛因后，雌性寻求海洛因的程度更高，而不是连续接触海洛因，这种影响与发情周期无关。大鼠的间歇性海洛因获取类似于海洛因使用障碍的关键特征：一种自我给药模式，其特征是反复使用大剂量海洛因，在早期戒断期间更容易复发。这对于完善物质使用障碍的动物模型和更好地理解导致这种疾病的神经适应具有重要意义。
Studies using intermittent access drug self-administration show increased motivation to take and seek cocaine and fentanyl, relative to continuous access. In this study, we examined the effects of intermittent- and continuous access self-administration on heroin intake, patterns of self-administration, and cue-induced heroin seeking, after forced or voluntary abstinence, in male and female rats. We also modeled brain levels of heroin and its active metabolites. Rats were trained to self-administer a palatable solution and then heroin (0.075 mg/kg/inf) either continuously (6-h/d; 10 d) or intermittently (6-h/d; 5-min access/30-min; 10 d). Brain levels of heroin and its metabolites were modeled using a pharmacokinetic software. Next, heroin-seeking was assessed after 1 or 21 abstinence days. Between tests, rats underwent either forced or voluntary abstinence. The estrous cycle was measured using a vaginal smear test. Intermittent access exacerbated heroin self-administration and was characterized by a burst-like intake, yielding higher brain peaks of heroin and 6-monoacetylmorphine concentrations. Moreover, intermittent access increased cue-induced heroin-seeking during early, but not late abstinence. Heroin-seeking was higher in females after intermittent, but not continuous access and this effect was independent of the estrous cycle. Intermittent heroin access in rats resembles critical features of heroin use disorder: a self-administration pattern characterized by repeated large doses of heroin and higher relapse vulnerability during early abstinence. This has significant implications for refining animal models of substance use disorder and for better understanding of the neuroadaptations responsible for this disorder.
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影响因子：
10.6
作者：
Caprioli D;Venniro M;Zeric T;Li X;Adhikary S;Madangopal R;Marchant NJ;Lucantonio F;Schoenbaum G;Bossert JM;Shaham Y
通讯作者：
Shaham Y
DOI：
10.1523/jneurosci.1914-12.2012
发表时间：
2012-08-22
期刊：
The Journal of neuroscience : the official journal of the Society for Neuroscience
影响因子：
--
作者：
Fanous S;Goldart EM;Theberge FR;Bossert JM;Shaham Y;Hope BT
通讯作者：
Hope BT
影响因子：
4.2
作者：
Epstein, David H.;Schmittner, John;Umbricht, Annie;Schroeder, Jennifer R.;Moolchan, Eric T.;Preston, Kenzie L.
通讯作者：
Preston, Kenzie L.
影响因子：
4.1
作者：
AZRIN, NH
通讯作者：
AZRIN, NH
影响因子：
7.3
作者：
Alexander, Stephen P. H.;Kelly, Eamonn;Davies, Jamie A.
通讯作者：
Davies, Jamie A.