Behavioral effects of several new anxiolytics and putative anxiolytics

The behavioral effects of several new anxiolytics and putative anxiolytics were evaluated in two tests sensitive for anxiolytic activity. In the first test, rats were trained to lever-respond for sweetened milk under a multiple variable-interval fixed-ratio (VI-FR) schedule of reinforcement. In the FR component a brief electric shock coincided with the presentation of reward (i.e. conflict procedure). Treatment of these rats with diazepam, tracazolate, CGS-9896, and the pyrimidinylpiperazine derivatives buspirone, gepirone and ipsapirone (TVX Q 7821) significantly increased responding that was suppressed by foot-shock. A common metabolite of the pyrimidinylpiperazines, l-PP, had no affect on punished responding. A second group of rats was trained to discriminate diazepam from saline using a two-lever operant choice procedure. Diazepam-stimulus generalization occurred to CGS-9896, CL 218,872, zopiclone and tracazolate, but not to buspirone, gepirone, ipsapirone or l-PP. It was concluded that while all of the new compounds examined appear to share an anxiolytic effect as demonstrated by their activity in the conflict procedure, the pyrimidinylpiperazine agents do not share discriminative stimulus properties which are common to drugs which act via the benzodiazepine receptor.