Department of Psychiatry, University of Minnesota, Minneapolis, MN 55455, USA.
Drug Alcohol Depend. 2012 Jan 1;120(1-3):233-7. doi: 10.1016/j.drugalcdep.2011.07.010. Epub 2011 Aug 5.
Sex differences in methamphetamine (METH) use (females>males) have been demonstrated in clinical and preclinical studies. This experiment investigated the effect of sex on the reinstatement of METH-seeking behavior in rats and determined whether pharmacological interventions for METH-seeking vary by sex. Treatment drugs were modafinil (MOD), an analeptic, and allopregnanolone (ALLO), a neuroactive steroid and progesterone metabolite.
Male and female rats were trained to self-administer i.v. infusions of METH (0.05 mg/kg/infusion). Next, rats self-administered METH for a 10-day maintenance period. METH was then replaced with saline, and rats extinguished lever-pressing behavior over 18 days. A multi-component reinstatement procedure followed whereby priming injections of METH (1mg/kg) were administered at the start of each daily session, preceded 30 min by MOD (128 mg/kg, i.p.), ALLO (15 mg/kg, s.c.), or vehicle treatment. MOD was also administered at the onset of the session to determine if it would induce the reinstatement of METH-seeking behavior.
Female rats had greater METH-induced reinstatement responding compared to male rats following control treatment injections. MOD (compared to the DMSO control) attenuated METH-seeking behavior in male and female rats; however, ALLO only reduced METH-primed responding in females. MOD alone did not induce the reinstatement of METH-seeking behavior.
These results support previous findings that females are more susceptible to stimulant abuse compared to males, and ALLO effectively reduced METH-primed reinstatement in females. Further, results illustrate the utility of MOD as a potential agent for prevention of relapse to METH use in both males and females.
在临床和临床前研究中已经证明，男性和女性在使用冰毒（METH）方面存在性别差异（女性>男性）。本实验研究了性别的影响对大鼠寻求 METH 行为的复吸的影响，并确定了针对 METH 寻求的药物干预是否因性别而异。治疗药物为莫达非尼（MOD），一种兴奋剂，和别孕烯醇酮（ALLO），一种神经活性甾体和孕酮代谢物。
雄性和雌性大鼠接受训练，可进行静脉内 METH（0.05mg/kg/输注）的自我给药。接下来，大鼠进行 METH 的 10 天维持期自我给药。然后用生理盐水替代 METH，大鼠在 18 天内消退了压杆行为。然后进行了多成分复吸程序，即在每天的开始时给予 METH（1mg/kg）的引发注射，30 分钟前给予 MOD（128mg/kg，ip），ALLO（15mg/kg，sc）或载体处理。MOD 也在会议开始时给药，以确定它是否会引发 METH 寻求行为的复吸。
与对照处理注射相比，雌性大鼠在控制处理后，METH 诱导的复吸反应更强。与 DMSO 对照相比，MOD（与 DMSO 对照相比）减弱了雄性和雌性大鼠的 METH 寻求行为；然而，ALLO 仅降低了雌性动物的 METH 引发的反应。MOD 本身不会引起 METH 寻求行为的复吸。
这些结果支持了先前的研究结果，即女性比男性更容易滥用兴奋剂，并且 ALLO 有效减少了女性的 METH 引发的复吸。此外，结果表明 MOD 作为一种预防男性和女性对 METH 使用复发的潜在药物的有效性。
