NITRIC-OXIDE SYNTHASE INHIBITORS PRODUCE PHENCYCLIDINE-LIKE BEHAVIORAL-EFFECTS IN PIGEONS

The present study assessed the ability of nitric oxide synthase (NOS) inhibitors to produce PCP-like behavioral effects in pigeons. Food-res tricted pigeons were trained to discriminate between PCP (1.0 mg/kg, i .m.) from saline in a two-key operant procedure. NOS inhibitors 7-nitr oindazole (7-NI) and N-omega-nitro-L-arginine methyl ester (L-NAME) pr oduced PCP like discriminative stimulus effects. 7-NI (17.8 mg/kg, i.m .) completely generalized to PCP. L-NAME (320-1000 mg/kg) produced par tial generalization to PCP. D-NAME, the enantiomer of L-NAME, did not produce PCP-appropriate behavior. L-NAME was approximately 200-times m ore potent i.c.v., but did not fully generalize to PCP. Both NOS inhib itors were effective in producing catalepsy, which is an effect common ly produced by competitive and uncompetitive NMDA antagonists. 7-NI (3 2 mg/kg) produced catalepsy in all subjects, whereas L-NAME (3200 mg/k g) produced catalepsy in 50% of the subjects. D-NAME did not produce c atalepsy. Pretreatment with L-arginine (32-3200 mg/kg) prevented the P CP-like discriminative stimulus and cataleptic effects of 7-NI (17.8-3 2 mg/kg), demonstrating that 7-NI produced PCP-like effects through bl ockade of NO synthesis. The current studies reveal that NOS inhibitors induced two behavioral actions, discriminative stimulus effects and c atalepsy, that are very selective for NMDA antagonists in pigeons.