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Anti‐conflict effects of triazolam‐pregnanolone combinations in rhesus monkeys
Author(s) -
Fischer Bradford D,
Rowlett James K
Publication year - 2010
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.24.1_supplement.767.1
Subject(s) - triazolam , pregnanolone , neuroactive steroid , chemistry , benzodiazepine , endocrinology , pharmacology , gabaa receptor , medicine , receptor , biochemistry
Positive modulators at benzodiazepine (BZ) and neuroactive steroid sites on GABA A receptors interact in an additive or supra‐additive manner depending on the experimental endpoint. The present study examined the combined effects of the BZ triazolam and the neuroactive steroid pregnanolone in a conflict procedure. Rhesus monkeys were trained on a multiple schedule of food presentation in the absence (non‐suppressed responding) and presence of response contingent electric shock (suppressed responding). When administered alone, triazolam and pregnanolone both decreased rates of non‐suppressed responding. Fixed ratio mixtures 1:30, 1:100, and 1:300 triazolam:pregnanolone also decreased rates of non‐suppressed responding, and did so in an additive manner. In contrast, triazolam produced dose‐dependent increases in rates of suppressed responding, whereas pregnanolone failed to produce an effect. Fixed ratio mixtures 1:30, 1:100, and 1:300 triazolam:pregnanolone also produced dose‐dependent increases in rates of suppressed responding. Here, the 1:30 triazolam:pregnanolone mixture resulted in an additive effect; however, the 1:100 and 1:300 mixtures induced significant supra‐additive effects. These results suggest that pregnanolone selectively enhances the anti‐conflict effects of triazolam, which raises the possibility that neuroactive steroids potentiate the anxiolytic effects of BZs.