Gabriel Kara I, Cunningham Christopher L, Finn Deborah A
Department of Behavioral Neuroscience, Oregon Health & Science University, 3181 SW Sam Jackson Park Road, Portland, OR 97239, USA.
Psychopharmacology (Berl). 2004 Oct;176(1):50-6. doi: 10.1007/s00213-004-1862-2. Epub 2004 Apr 9.
The neurosteroid allopregnanolone (ALLOP; 3alpha-hydroxy-5alpha-pregnan-20-one) produces behavioral and discriminative characteristics similar to that of ethanol (EtOH) and can modulate some of the behavioral and electrophysiological effects of EtOH.
The present experiments investigated ALLOP modulation of the effects of EtOH in a place conditioning procedure in male DBA/2J mice.
In a series of experiments examining different EtOH doses (1, 2 g/kg) and ALLOP administration times, ALLOP (0, 3.2, 10, 17 mg/kg, i.p.) was administered four times with EtOH prior to placement on a distinctive floor (CS+). On alternate days, vehicle was administered prior to a saline injection paired with the other floor stimulus (CS-). In a separate experiment, finasteride (0, 50, 100 mg/kg, i.p.), a 5alpha-reductase inhibitor that blocks ALLOP synthesis, was administered prior to both CS+ and CS- trials. In a final experiment, animals were place conditioned to EtOH alone, and ALLOP (0, 3.2, 10, 17 mg/kg, i.p.) was administered prior to the preference test only.
During conditioning, ALLOP increased and finasteride decreased EtOH-stimulated activity compared with vehicle pretreatment. Acquisition of 2 g/kg EtOH-induced conditioned place preference was observed in all mice, regardless of treatment with either ALLOP or finasteride. Similarly, ALLOP did not modulate the expression of EtOH-induced place preference. EtOH increased brain ALLOP levels compared with saline; however, ALLOP administration produced dose-dependent elevations in brain ALLOP levels that were not further augmented by EtOH (2 g/kg) administration.
These findings indicate that ALLOP does not modulate EtOH-induced place conditioning in male DBA/2J mice.
神经甾体别孕烯醇酮（ALLOP；3α-羟基-5α-孕烷-20-酮）产生的行为和辨别特征与乙醇（EtOH）相似，并且可以调节EtOH的一些行为和电生理效应。
本实验在雄性DBA/2J小鼠的位置条件反射实验中研究了ALLOP对EtOH效应的调节作用。
在一系列实验中，研究了不同EtOH剂量（1、2 g/kg）和ALLOP给药时间，在将小鼠放置在独特地板（CS+）之前，ALLOP（0、3.2、10、17 mg/kg，腹腔注射）与EtOH一起给药四次。在交替的日子里，在与另一个地板刺激（CS-）配对的盐水注射之前给予赋形剂。在另一个实验中，在CS+和CS-试验之前给予非那雄胺（0、50、100 mg/kg，腹腔注射），一种阻断ALLOP合成的5α-还原酶抑制剂。在最后一个实验中，动物仅对EtOH进行位置条件反射，并且仅在偏好测试之前给予ALLOP（0、3.2、10、17 mg/kg，腹腔注射）。
在条件反射过程中，与赋形剂预处理相比，ALLOP增加而菲那雄胺降低了EtOH刺激的活动。无论用ALLOP还是非那雄胺处理，所有小鼠均观察到2 g/kg EtOH诱导的条件性位置偏好的获得。同样，ALLOP没有调节EtOH诱导的位置偏好的表达。与盐水相比，EtOH增加了脑内ALLOP水平；然而，给予ALLOP导致脑内ALLOP水平呈剂量依赖性升高，而给予EtOH（2 g/kg）并未使其进一步升高。
这些发现表明，ALLOP不会调节雄性DBA/2J小鼠中EtOH诱导的位置条件反射。
