Evaluation of the effects of PD 134308 (CI-988), a CCK-B antagonist, on the punished responding of squirrel monkeys.

Lever pressing of squirrel monkeys was maintained by a fixed-interval 3-min schedule of food presentation during which every 30th response also produced a brief electric shock. Lever pressing was suppressed during this stimulus (conflict or punishment) compared to that occurring prior to the introduction of shock or, with some monkeys, during an alternate stimulus in which punishment did not occur. PD 134308 (CI-988), administered i.m. (0.03-3.0 mg/kg), increased punished responding but had no effect on non-punished responding. Peak increases of 150% of control occurred at 3.0 mg/kg. There was no indication of sedation at the highest dose of PD 134308 (10.0 mg/kg). By comparison, chlordiazepoxide (1.0-10 mg/kg, i.m.) produced similar effects, except the magnitude of increases in punished responding reached approximately 200% of control performance levels and the higher doses reduced non-punished response rates. PD 134308 produces anxiolytic-like effects in this animal model of anxiety that would suggest potential clinical efficacy in humans of a novel class of compounds with actions at or modulated by cholecystokinin receptors.