Effects of allopregnanolone on the reinstatement of cocaine-seeking behavior in male and female rats
Effects of allopregnanolone on the reinstatement of cocaine-seeking behavior in male and female rats
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DOI：
10.1007/s00213-008-1371-9
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发表时间：
2009-03-01
影响因子：
3.4
通讯作者：
Carroll, Marilyn E.
中科院分区：
文献类型：
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作者：
Anker, Justin J.;Holtz, Nathan A.;Carroll, Marilyn E.
先前的研究表明，孕酮(PROG)减少了雌性大鼠的可卡因寻求行为。Prog的这种作用可能部分是由于其代谢物别孕酮(allopregnanolone，Allo)，它已被证明能降低可卡因的致敏作用，并降低与可卡因过量有关的致死性。本研究的目的是观察Allo对雌性和雄性大鼠恢复寻找可卡因行为的影响。注射可卡因(每次0.4 mg/kg)，持续2小时，一旦达到获得标准，持续给药14天。然后用生理盐水取代可卡因，并允许杠杆按压在21天内熄灭。消失期后，给大鼠皮下注射。Allo(15或30 mg/kg)、Prog(0.5 mg/kg)、Prog(0.5 mg/kg)加5-α还原酶抑制剂非那雄胺(25 mg/kg)或赋形剂预处理3d。然后用三种剂量的可卡因(5、10和15 mg/kg，i.p)对大鼠进行恢复试验。PROG和ALLO在更大程度上减少了可卡因诱导的雌性动物的恢复，而非那雄胺则阻断了PROG对恢复的减弱作用。Allo对男性可卡因诱导的复吸没有影响。这些发现表明，Allo可能部分解释了Prog对可卡因诱导的复吸的抑制作用，这可能是预防女性可卡因滥用者复发的一种新方法。
Previous research indicates that progesterone (PROG) decreased cocaine-seeking behavior in female rats. This effect of PROG may be in part due to its metabolite allopregnanolone (ALLO), which has been shown to decrease the sensitizing effects of cocaine and reduce lethality associated with cocaine overdose in mice.The purpose of the present study was to examine the effects of ALLO on the reinstatement of cocaine-seeking behavior in female and male rats.Rats were trained to lever press for i.v. infusions of cocaine (0.4 mg/kg per infusion) during 2-h sessions, and once acquisition criteria were met, cocaine self-administration continued for 14 days. Cocaine was then replaced with saline, and lever pressing was allowed to extinguish over 21 days. After the extinction phase, rats received s.c. ALLO (15 or 30 mg/kg), PROG (0.5 mg/kg), PROG (0.5 mg/kg) plus the 5-alpha reductase inhibitor finasteride (25 mg/kg), or vehicle pretreatment for 3 days. Rats were then tested during reinstatement with three doses of cocaine (5, 10, and 15 mg/kg, i.p. in mixed order).PROG, and to a greater extent ALLO, decreased cocaine-primed reinstatement in females, while finasteride blocked the attenuating effects of PROG on reinstatement. ALLO had no effect on cocaine-primed reinstatement in males.These findings suggest that ALLO may explain part of PROG's inhibitory effect on cocaine-primed reinstatement, and it may serve as a novel approach for preventing relapse in female cocaine abusers.