Effects of alpha-methyl-p-tyrosine, adrenolytic compounds, pimozide and other neuroleptics, on the narcotic cue

Abstract

Using a two-lever food-reinforced operant procedure, rats (n=11) were trained to discriminate the narcotic analgesic fentanyl (0.04 mg/kg, s.c.) from saline. In rats so trained, alpha methyl-p-tyrosine (150 mg/kg, i.p.) was found not to affect the discriminability of fentanyl. Pretreatment (s.c.) with either adrenolytic compounds (10 mg/kg aceperone, 40 mg/kg dibenamine, 10 mg/kg phenoxybenzamine, 20 mg/kg propranolol) or sedative neuroleptics (0.63 mg/kg azaperone, 1.25 mg/kg chlorpromazine, 10 mg/kg pipamperone) likewise failed to attenuate the narcotic cue. Pimozide (0.63 mg/kg) and, to some extent, spiperone (0.04 mg/kg) reduced the percentage of responding on the selected lever, and pimozide antagonized drug lever selection in some animals. The results suggest that specific neuroleptics (e.g. pimozide) may affect the subjective effects induced by narcotics in humans.