Methamphetamine (METH) abuse is characterised by chronic relapse and anxiety, for which there are no effective pharmacotherapies. Acute treatment with the neuropeptide oxytocin has shown therapeutic potential for METH addiction and has social and anxiolytic effects in METH-naïve rats. However, the effects of chronic oxytocin treatment in METH-experienced rats are unknown. This study investigated the effects of repeated oxytocin treatment during abstinence from METH self-administration on incubation of cue-induced relapse, yohimbine- and METH-induced reinstatement, trait anxiety, and social interaction. Male and female Sprague-Dawley rats self-administered intravenous METH for 2 h/day (12 days) and then on short-access (2 h/day; ShA) or long-access (6 h/day; LgA) sessions (10 days). Rats underwent 30 days of drug abstinence, during which they received 15 days of intraperitoneal oxytocin (1 mg/kg) or saline (days 6-20) injections. Anxiety and social interaction were tested on days 25-28, and incubation was assessed by testing cue-induced relapse on days 2 and 30. Rats underwent extinction after the final cue-relapse test, followed by yohimbine- and METH-primed reinstatement. LgA, but not ShA rats exhibited incubation of METH-craving and enhanced METH-primed reinstatement in both sexes, and enhanced yohimbine-induced reinstatement in females. Importantly, chronic oxytocin attenuated incubation and METH-primed reinstatement in both sexes, and yohimbine-induced reinstatement in females, although only in LgA rats. LgA produced a heightened anxiety phenotype, which was partially rescued by chronic oxytocin treatment. Using a translatable addiction model, these findings demonstrate the therapeutic efficacy of chronic oxytocin after METH self-administration and supports the clinical utility of oxytocin for METH addiction in both sexes.

中文翻译：

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甲基苯丙胺自我给药禁欲期间的长期催产素治疗对渴望，恢复和焦虑的潜伏期的影响。

甲基苯丙胺（METH）的滥用具有慢性复发和焦虑的特点，目前尚无有效的药物治疗方法。用神经肽催产素进行的急性治疗已显示出对METH成瘾的治疗潜力，并且在未使用METH的大鼠中具有社交和抗焦虑作用。但是，长期服用催产素在METH经验丰富的大鼠中的作用尚不清楚。这项研究调查了在自我禁食METH期间重复催产素治疗对孵化所诱导的复发，育亨宾和METH诱导的恢复，特质焦虑和社交互动的影响。雄性和雌性Sprague-Dawley大鼠自行静脉注射METH，持续2 h /天（12天），然后短期（2 h /天； ShA）或长时间（6 h /天； LgA）（10次）天）。大鼠禁食30天，在此期间，他们接受了15天的腹腔内催产素（1 mg / kg）或生理盐水（第6-20天）注射。在第25-28天测试了焦虑和社交互动，并通过在第2天和第30天测试提示诱发的复发来评估潜伏期。在最后的提示复发测试后，大鼠经历了灭绝，随后进行了育亨宾和METH引发的恢复。LgA，但不是ShA大鼠表现出对METH渴望的孵化，并在两性中增强了METH引发的恢复，并且在雌性中增强了育亨宾诱导的恢复。重要的是，尽管仅在LgA大鼠中，慢性催产素减弱了雌性的温育和METH引发的恢复，雌性育亨宾诱导的恢复。LgA产生增强的焦虑表型，其通过慢性催产素治疗得以部分挽救。使用可翻译的成瘾模型，