INTERACTIONS OF BUSPIRONE OR GEPIRONE WITH NICOTINE ON SCHEDULE-CONTROLLED BEHAVIOR OF PIGEONS

The primary purpose of the present study was to examine the interactio n of buspirone with nicotine in pigeons responding under a fixed-ratio 30 schedule of food presentation. The hypothesis was that the dopamin e D2 receptor antagonist activity of buspirone would attenuate the rat e-decreasing effects of nicotine. When administered alone, buspirone ( 0.3-10 mg/kg) and (-) -nicotine (0.1-3.0 mg/kg) decreased response rat es in a dose-related manner, with ED50 values (+/- 95% C.L.) of 3.0 (1 .7-5.1) mg/kg and 1.0 (0.7-1.5) mg/kg, respectively. Low doses of busp irone (0.3-1.0 mg/kg) did not significantly shift the nicotine dose-re sponse function, while doses of buspirone (3.0-10 mg/kg) that produced rate-decreasing effects shifted the nicotine dose-response function t o the left. There was no significant statistical interaction between b uspirone and nicotine indicating that the shifts in the nicotine dose- response function were parallel. The buspirone analog gepirone (0.3-10 mg/kg), which like buspirone is a serotonin (5-HT1A) agonist, but unl ike buspirone is relatively devoid of D2 antagonist activity, was also tested in combination with nicotine. Gepirone was less potent in decr easing response rates compared with buspirone, with an ED50 value of 4 .5 (3.1-6.7) mg/kg. Rate-decreasing doses of gepirone (3.0-10 mg/kg) i n combination with nicotine resulted in parallel shifts to the left of the nicotine dose-response function. There was no statistically signi ficant difference between the effects of buspirone and those of gepiro ne on the nicotine dose-response function. Isobolograms indicated that the pharmacological interactions between buspirone or gepirone and ni cotine were not different from additivity. These results suggest that the combined effects of buspirone and nicotine on schedule-controlled behavior are independent of antagonism at D2 receptors.