Discriminative stimulus effects of pregnanolone in rats: role of training dose in determining mechanism of action.
Discriminative stimulus effects of pregnanolone in rats: role of training dose in determining mechanism of action.
复制标题
孕烯醇酮对大鼠的辨别刺激作用：训练剂量在确定作用机制中的作用。
DOI：
10.1007/s00213-012-2701-5
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发表时间：
2012
影响因子：
3.4
通讯作者：
Gerak,LisaR
中科院分区：
文献类型：
--
作者：
Eppolito,AmyK;Bai,Xiang;Gerak,LisaR
RationalePositive γ-aminobutyric acidA(GABAA) modulators acting at different binding sites often produce similar behavioral effects; however, their effects are not identical. Actions of neuroactive steroids at other receptors, in addition to GABAAreceptors, might account for some differences between neuroactive steroids and other positive modulators, like benzodiazepines.ObjectiveMultiple mechanisms of other drugs (e.g., ethanol) have been elucidated by comparing their discriminative stimulus effects across different training doses; the current study used that approach to examine the mechanisms of action of the neuroactive steroid pregnanolone.MethodsSeparate groups of rats (n= 6–8/group) discriminated pregnanolone from vehicle while responding under a fixed-ratio 10 schedule of food presentation. Two groups initially discriminated 3.2 mg/kg; once stimulus control was established, the training dose was systematically decreased to 1.33 mg/kg in one group and increased to 7.5 mg/kg in the other group. Other rats discriminated either 1.33 or 7.5 mg/kg without training at another dose.ResultsStimulus control was established in 24–28 sessions in all groups. Positive GABAAmodulators produced ≥80 % pregnanolone-lever responding, regardless of training dose; rank-order potency was flunitrazepam > midazolam > pregnanolone = pentobarbital. Ethanol produced some drug-lever responding (42 %) only in rats discriminating 1.33 mg/kg, whereas theN-methyl-d-aspartate receptor antagonist ketamine and the serotonin receptor agonist 1-(m-chlorophenyl)-biguanide occasioned predominantly vehicle-lever responding in all rats.ConclusionsThere was little difference in discriminative stimulus effects of pregnanolone across different training conditions, confirming a predominant, if not exclusive, role of GABAAreceptors in these effects of pregnanolone.
