Pizotifen (BC-105) attenuates orienting and Pavlovian heart rate conditioning in rabbits.

The cardiac component of the orienting reflex (OR) was elicited in rabbits by 75 dB, 4-sec duration tones of either 304 or 1216 Hz. The conditioned cardiac response was also studied using the same tones and paraorbital electric shock as conditioned and unconditioned stimuli, respectively, using a differential Pavlovian conditioning paradigm. Subcutaneous injections of the central 5-HT antagonist pizotifen (BC-105), the peripheral 5-HT antagonist xylamidine, the central 5-HT agonist d-lysergic acid diethylamide (LSD), and LSD in conjunction with BC-105 were administered 15 min prior to behavioral assessment. Both the heart rate (HR) conditioned response (CR) and the OR consisted of bradycardia. BC-105 attenuated, but xylamidine had no effect on, OR habituation. LSD reduced the magnitude of the OR, an effect which was blocked by BC-105. BC-105 also produced a dose-related attenuation of the bradycardiac HR CR; however, xylamidine had no effect on HR conditioning, suggesting that the attenuation of the HR CR by BC-105 was central rather than peripheral in origin. LSD potentiated the bradycardiac HR CR, but BC-105 in conjunction with LSD attenuated this response. These results suggest that central 5-HT neurons may modulate the magnitude of bradycardiac responses during orienting and aversive Pavlovian conditioning.