Rolipram as a discriminative stimuli: transfer to phosphodiesterase inhibitors

Rats were trained to discriminate (+/-)-rolipram (0.32 mg/kg, i.p.) from saline in a two-lever food-reinforced drug discrimination procedure (FR 10). (+/-)-Rolipram served as a drug discriminative stimulus, and its discrimination was readily established with a mean of 42 training sessions to achieve criterion performance (at least 80% correct response in the consecutive generalization tests with both saline and (+/-)-rolipram). Thereafter, this stimulus was stably maintained. The (-)-isomer of rolipram was generalized at about one-third of the training dose of the (+/-)-compound, but the (+)-isomer was generalized only at 10 times the dose of the (+/-)-compound. This finding suggests that the (-)-compound is more extensively involved as a stimulus than either (+/-)-rolipram or the (+)-isomer. Ro20-1724, caffeine and theophylline, which are phosphodiesterase inhibitors, were generalized to (+/-)-rolipram. This result strongly suggests that phosphodiesterase inhibition may be an important factor involved in (+/-)-rolipram discrimination.