Antipunishment activity of diazepam in rats trained to discriminate diazepam from vehicle.

Abstract

The anxiolytic and discriminative stimulus effects of drugs in the same rats during a single session were examined in this study. Rats were trained to discriminate diazepam (5 mg/kg) from vehicle in a 2-lever drug discrimination procedure and were then trained to press a 3rd lever under a multiple fixed-interval (60 sec), fixed-ratio 5 + shock schedule of food reward. Diazepam produced substitution for itself in all rats; however, it produced antipunishment effects in some of the rats, suggesting that its discriminative stimulus and antipunishment effects are separable. In contrast, the N-methyl-D-aspartate antagonists, NPC 17742 and phencyclidine, failed to substitute fully for diazepam and did not increase punished responding in any of the rats. These results are consistent with those of studies showing that drugs from this class produce weaker antipunishment effects than diazepam does. The potential utility of this new method is that it allows direct comparisons of the antipunishment and discriminative stimulus effects of putative anxiolytic drugs during a single session with the same animals.

Effects of modulators of N-methyl-D-aspartate receptor-mediated neurotransmission on diazepam discrimination in rats

“…Whereas diazepam fully substituted for itself at a dose that did not substantially alter response rates, NPC 17742 substituted only partially and did so at a dose that significantly decreased overall responding. These results are consistent with a previous study in our lab in which NPC 17742 partially substituted for diazepam at response-rate decreasing doses in a combination diazepam discrimination / conflict procedure paradigm (Wiley and Balster, 1999). Further, while benzodiazepines cross-substitute for each other in drug discrimination studies (Young and Glennon, 1987), diazepam did not generalize from NPC 12626 (the racemate of which NPC 17742 is an isomer) in rats trained to discriminate this drug from vehicle (Bobelis and Balster, 1993).…”