Using drug combinations to assess potential contributions of non-GABAA receptors in the discriminative stimulus effects of the neuroactive steroid pregnanolone in rats.
Using drug combinations to assess potential contributions of non-GABAA receptors in the discriminative stimulus effects of the neuroactive steroid pregnanolone in rats.
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使用药物组合来评估非 GABAA 受体在大鼠神经活性类固醇孕烯醇酮的辨别刺激作用中的潜在贡献。
DOI：
10.1016/j.physbeh.2014.07.003
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发表时间：
2014
影响因子：
2.9
通讯作者：
Gerak,LisaR
中科院分区：
文献类型：
--
作者：
Eppolito,AmyK;Kodeih,HannaR;Gerak,LisaR
Neuroactive steroids are increasingly implicated in the development of depression and anxiety and have been suggested as possible treatments for these disorders. While neuroactive steroids, such as pregnanolone, act primarily at γ-aminobutyric acidA(GABAA) receptors, other mechanisms might contribute to their behavioral effects and could increase their clinical effectiveness, as compared with drugs acting exclusively at GABAAreceptors (e.g., benzodiazepines). The current study examined the role of non-GABAAreceptors, including N-methyl-d-aspartate (NMDA) and serotonin3(5-HT3) receptors, in the discriminative stimulus effects of pregnanolone. Separate groups of rats discriminated either 3.2 mg/kg pregnanolone from vehicle or 0.32 mg/kg of the benzodiazepine midazolam from vehicle while responding under a fixed-ratio 10 schedule for food pellets. When administered alone in both groups, pregnanolone and midazolam produced ≥ 80% drug-lever responding, the NMDA receptor antagonists dizocilpine and phencyclidine produced ≥ 60 and ≥ 30% drug-lever responding, respectively, and the 5-HT3receptor agonist 1-(m-chlorophenyl)-biguanide (CPBG) and morphine produced < 20% drug-lever responding up to doses that markedly decreased response rates. When studied together, neither dizocilpine, phencyclidine, CPBG nor morphine significantly altered the midazolam dose–effect curve in either group. Given that CPBG is without effect, it is unlikely that 5-HT3receptors contribute substantially to the discriminative stimulus effects of pregnanolone. Similarities across groups in effects of dizocilpine and phencyclidine suggest that NMDA receptors do not differentially contribute to the effects of pregnanolone. Thus, NMDA and 5-HT3receptors are not involved in the discriminative stimulus effects of pregnanolone.
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