Comparing the discriminative stimuli produced by either the neuroactive steroid pregnanolone or the benzodiazepine midazolam in rats.
Comparing the discriminative stimuli produced by either the neuroactive steroid pregnanolone or the benzodiazepine midazolam in rats.
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DOI：
10.1007/s00213-010-2047-9
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发表时间：
2011-03
影响因子：
3.4
通讯作者：
Gerak, Lisa R.
中科院分区：
文献类型：
--
作者：
Bai, Xiang;Gerak, Lisa R.
Neuroactive steroids might be therapeutic alternatives for benzodiazepines because they have similar anxiolytic, sedative and anticonvulsant effects, and their actions at different modulatory sites on GABAA receptors might confer differences in adverse effects. This study used drug discrimination to compare discriminative stimuli produced by positive GABAA modulators that vary in their site of action on GABAA receptors. Two groups of rats discriminated either 3.2 mg/kg of pregnanolone or 0.56 mg/kg of midazolam from vehicle while responding under a fixed ratio 10 schedule of food presentation. Pregnanolone, midazolam and flunitrazepam produced ≥80% drug-lever responding in both groups; each drug was more potent in rats discriminating pregnanolone. Pentobarbital produced ≥80% drug-lever responding in all rats discriminating pregnanolone and in 1/3 of the rats discriminating midazolam with larger doses decreasing response rates to <20% of control. Morphine and ketamine produced predominantly saline-lever responding in both groups. Flumazenil antagonized midazolam and flunitrazepam in both groups; slopes of Schild plots were not different from unity and pA2 values for flumazenil ranged from 5.86 to 6.09. Flumazenil did not attenuate the discriminative stimulus effects of pregnanolone. The midazolam and pregnanolone discriminative stimuli were qualitatively similar, although the effects of pentobarbital were not identical in the two groups. Although acute effects of midazolam and pregnanolone are similar, suggesting that neuroactive steroids might retain the therapeutic effects of benzodiazepines, differences emerge during chronic treatment, indicating that neuroactive steroids might produce fewer adverse effects than benzodiazepines.
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影响因子：
13.8
作者：
DOBLE, A;MARTIN, IL
通讯作者：
MARTIN, IL
影响因子：
3.4
作者：
Gerak, Lisa R.
通讯作者：
Gerak, Lisa R.
影响因子：
4.3
作者：
Lader, Malcolm
通讯作者：
Lader, Malcolm
影响因子：
2.9
作者：
GONSALVES, SF;GALLAGER, DW
通讯作者：
GALLAGER, DW
影响因子：
5
作者：
Brot, MD;Akwa, Y;Britton, KT
通讯作者：
Britton, KT