Department of Neurosciences, Medical University of South Carolina, Charleston, SC 29425, USA.
Psychoneuroendocrinology. 2013 Oct;38(10):2343-53. doi: 10.1016/j.psyneuen.2013.05.005. Epub 2013 Jun 12.
Previous evidence in an animal model of drug self-administration and drug seeking showed that acute oxytocin decreased methamphetamine (meth) seeking in male rats, suggesting potential clinical efficacy for the treatment of psychostimulant addiction. However, based on the well-established role of oxytocin in reproduction and pair bond formation, it is important to know how this effect extrapolates to females. Here, we tested whether oxytocin (1mg/kg, IP) would decrease meth seeking in female rats across various stages of the estrous cycle (Experiment 1). Freely cycling Long Evans female rats self-administered meth (IV) in 2-h daily sessions, followed by daily extinction sessions. Following extinction, rats received oxytocin (0, 0.3, or 1mg/kg, IP) 30min before a meth priming injection (1mg/kg, IP) to assess reinstatement of meth seeking. Next, we examined the effects of oxytocin on motivated meth- and sucrose-taking and seeking in male and female rats. In separate experiments, males and females self-administered meth (Experiment 2) or sucrose (Experiment 3) until responding was stabilized along a fixed ratio (FR) 5 schedule of reinforcement. Subsequently, rats received either oxytocin or vehicle prior to self-administration along a progressive ratio (PR) schedule of reinforcement. Rats were subsequently tested for cue-, meth-, and stress-induced reinstatement after pretreatment with oxytocin or vehicle. While oxytocin reduced meth seeking in females, we found that estrous cycle stage (as determined from vaginal cytology) did not influence meth-primed reinstatement or the ability of oxytocin to decrease reinstatement of meth seeking. Oxytocin reduced PR responding for meth only in females. Females responded more than males during cue-induced reinstatement of meth and sucrose seeking, and oxytocin reduced this responding only in meth females. In both sexes, oxytocin attenuated meth seeking in response to a meth prime and yohimbine (a pharmacological stressor). The results suggest that oxytocin may have efficacy as a treatment of meth addiction in both sexes; however, females may show greater response to oxytocin treatment for the prevention of relapse.
先前在药物自我给药和觅药的动物模型中的证据表明，急性催产素可减少雄性大鼠对甲基苯丙胺（meth）的觅药，这表明其对治疗精神兴奋剂成瘾具有潜在的临床疗效。然而，基于催产素在生殖和伴侣关系形成中的既定作用，了解这种效应如何外推到雌性动物是很重要的。在这里，我们测试了催产素（1mg/kg，腹腔注射）是否会降低雌性大鼠在发情周期各个阶段对 meth 的觅药（实验 1）。自由循环的长耳雌性大鼠在 2 小时的每日给药期内自行注射 meth（IV），随后进行每日消瘾期。消瘾后，大鼠在接受 1mg/kg，腹腔注射的 meth 引发注射（1mg/kg，腹腔注射）前 30 分钟接受催产素（0、0.3 或 1mg/kg，腹腔注射），以评估 meth 觅药的恢复。接下来，我们研究了催产素对雄性和雌性大鼠对 meth 和蔗糖的动机性摄取和觅药的影响。在单独的实验中，雄性和雌性大鼠分别自行注射 meth（实验 2）或蔗糖（实验 3），直到反应在固定比率（FR）5 强化时间表上稳定。随后，大鼠在进行递增比率（PR）强化时间表的自我给药之前接受催产素或载体处理。随后，大鼠在接受催产素或载体预处理后进行线索、meth 和应激诱导的恢复测试。虽然催产素减少了雌性大鼠的 meth 觅药，但我们发现发情周期阶段（根据阴道细胞学确定）并不影响 meth 引发的恢复或催产素降低 meth 觅药恢复的能力。催产素仅减少了雌性大鼠的 PR 反应。在 meth 和蔗糖觅药的线索诱导恢复中，雌性大鼠的反应多于雄性大鼠，而催产素仅减少了 meth 雌性大鼠的反应。在两性中，催产素都可减轻对 meth 引发物和育亨宾（一种药理学应激源）的觅药。结果表明，催产素可能对两性的 meth 成瘾治疗有效；然而，女性可能对催产素治疗预防复发有更大的反应。
