PIZOTIFEN ATTENUATES CLASSICAL EYEBLINK AND HEART-RATE CONDITIONING IN RABBITS

Experimentally naive New Zealand albino rabbits received Pavlovian conditioning in which 75-dB, 500-msec-duration tones served as the conditioned stimulus and 200-msec paraorbital electric-shock trains served as the unconditioned stimulus. A pseudoconditioning control group received a random sequence of unpaired tones and shocks. Both eyeblink (EB) and heart rate (HR) conditioned responses (CRs) were assessed. Prior to each conditioning session, one of three doses (i.e., 2.5, 5.0, or 10 mg/kg) of pizotifen (BC105), a 5HT antagonist, or saline were administered subcutaneously. With all three doses of pizotifen, the acquisition of the eyeblink response was attenuated relative to that of animals that received saline injections. However, the lowest dose had the greatest effect and the highest dose the smallest effect; the middle dose produced an intermediate effect. The cardiac CR, which accompanied eyeblink conditioning, consisted of bradycardia and was also attenuated in a dose-related fashion by pizotifen. However, in this case, the largest dose had the greatest attenuating effect, the middle dose an intermediate effect, and the smallest dose the smallest effect. The group that received explicitly unpaired tones and shocks showed virtually no EB or HR conditioning. These results suggest that pizotifen may affect nonspecific processes related to autonomic conditioning, which in turn interferes with the acquisition of the somatomotor eyelid CR.