RT Journal Article
SR Electronic
T1 Anticonflict and Reinforcing Effects of Triazolam + Pregnanolone Combinations in Rhesus Monkeys
JF Journal of Pharmacology and Experimental Therapeutics
JO J Pharmacol Exp Ther
FD American Society for Pharmacology and Experimental Therapeutics
SP 805
OP 811
DO 10.1124/jpet.111.180422
VO 337
IS 3
A1 Bradford D. Fischer
A1 James K. Rowlett
YR 2011
UL http://jpet.aspetjournals.org/content/337/3/805.abstract
AB Combinations of positive modulators of benzodiazepine and neuroactive steroid sites on GABAA receptors have been shown to act in an additive or supra-additive manner depending on the endpoint under study, but they have not been assessed on experimentally induced conflict or drug self-administration. The present study examined the interactive effects of the benzodiazepine triazolam and the neuroactive steroid pregnanolone in a rhesus monkey conflict procedure (a model of anxiolysis) and on a progressive-ratio schedule of drug self-administration (a model of abuse potential). Both triazolam and pregnanolone decreased rates of nonsuppressed responding, whereas only triazolam consistently increased rates of suppressed responding (i.e., had an anticonflict effect). Fixed-ratio mixtures of triazolam and pregnanolone also decreased rates of nonsuppressed responding and did so in an additive manner. In contrast, mixtures of triazolam and pregnanolone produced either additive or supra-additive rate-increasing effects on suppressed responding, depending on the proportion of drugs in the mixture. Both triazolam and pregnanolone were self-administered significantly, and triazolam and pregnanolone mixtures had either proportion-dependent additive or infra-additive reinforcing effects. These results suggest that combinations of triazolam and pregnanolone may have enhanced anxiolytic effects with reduced behavioral disruption and abuse potential compared with either drug alone.