Department of Neurobiology and Anatomical Sciences, University of Mississippi Medical Center, Jackson, Mississippi, USA.
Department of Physiology and Biophysics, University of Mississippi Medical Center, Jackson, Mississippi, USA.
Neuropsychopharmacology. 2019 Feb;44(3):503-513. doi: 10.1038/s41386-018-0235-1. Epub 2018 Oct 6.
Vulnerability to develop addiction is influenced by numerous factors, including social behavior. Specifically, in human users, drug taking in a socio-sexual context appears to enhance further drug-seeking behavior. Users report heightened sexual pleasure as a motivation for further drug use and display risk behaviors even when tested in drug-free state. Here, using a preclinical model of limited voluntary drug use in rats, the hypothesis was tested that methamphetamine (Meth)-taking concurrently with socio-sexual experience increases vulnerability to addiction. Male Sprague Dawley rats were socially housed and underwent limited-access Meth self-administration (maximum 1 mg/kg/session). Meth-taking was either concurrent or non-concurrent with sexual behavior: concurrent animals were mated with a receptive female immediately after each session, while non-concurrent animals gained equivalent sexual experience the week prior. Next, drug-seeking behaviors were measured during cue reactivity, extinction, and reinstatement sessions using different extinction and reinstatement protocols in 4 separate studies. Both groups equally acquired Meth self-administration and did not differ in total Meth intake. However, drug-seeking behavior was significantly higher in concurrent animals during cue reactivity tasks, extinction sessions, and cue- or Meth-induced reinstatement tests. In addition, sexual behavior in the absence of Meth triggered reinstatement of drug-seeking in concurrent animals. These results indicate that Meth-taking in a socio-sexual context significantly enhances vulnerability for drug addiction in male rats. This preclinical paradigm of drug self-administration concurrent with socio-sexual behavior provides a useful model for studying the underlying neurobiology of socially driven vulnerability to drug addiction.
易患成瘾的倾向受到许多因素的影响，包括社会行为。具体而言，在人类使用者中，在社会性行为背景下使用药物似乎会增强进一步的觅药行为。使用者报告说，进一步使用药物的动机是性快感增强，并在未使用药物的状态下表现出冒险行为。在这里，使用大鼠有限自愿药物使用的临床前模型，检验了以下假设：在社会性行为体验的同时服用甲基苯丙胺（Meth）会增加成瘾的易感性。雄性 Sprague Dawley 大鼠群居饲养，并接受有限的 Meth 自我给药（每次 1mg/kg）。Meth 给药要么与性行为同时进行，要么不同时进行：同时给药的动物在每次给药后立即与一只接受的雌性动物交配，而非同时给药的动物在之前的一周获得相同的性经验。接下来，在 4 项不同的研究中使用不同的消退和重新激发方案，在线索反应、消退和重新激发期间测量药物寻求行为。两组动物均相等地获得了 Meth 自我给药，并且总 Meth 摄入量没有差异。然而，在线索反应任务、消退期间以及线索或 Meth 诱导的重新激发测试中，同时给药动物的药物寻求行为明显更高。此外，在没有 Meth 的情况下进行性活动会触发同时给药动物的药物寻求行为的重新激发。这些结果表明，在社会性行为背景下服用 Meth 会显著增强雄性大鼠对药物成瘾的易感性。这种同时进行药物自我给药和社会性行为的临床前模型为研究社会驱动的药物成瘾易感性的潜在神经生物学提供了一个有用的模型。
