ANTIPUNISHMENT EFFECTS OF ACUTE AND REPEATED ADMINISTRATION OF PHENCYCLIDINE AND NPC-12626 IN RATS

The effects of phencyclidine (PCP) and NPC 12626 on punished responding were examined using a modified Geller-Seifter procedure in rats. Both drugs are known to antagonize N-methyl-D-aspartate (NMDA) receptor mediated neurotransmission, albeit at different sites on the NMDA receptor complex. Rats were trained to lever press for food reinforcement under a multiple schedule, with responding in one component reinforced under a fixed-interval 60-sec schedule, while each response in the other component resulted in both food and brief electric shock. Both PCP and NPC 12626 produced selective increases in punished responding, although the effects were not as large as those produced by chlordiazepoxide. Repeated daily administration of each of these drugs for 6 days resulted in increases in punished responding during different portions of the treatment. A 5 mg/kg dose of chlordiazepoxide produced increases over the last 2 days of administration. PCP (2 mg/kg) produced an increase only during the second session, whereas NPC 12626 (30 mg/kg) produced increases for all but the first and fifth days of the 6-day regimen. Both competitive and noncompetitive NMDA antagonists can have antipunishment effects in this model.