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-restricted pigeons were trained to discriminate between PCP (1.0 mg/kg, i.m.) from saline in a two-key operant procedure. NOS inhibitors 7-nitroindazole (7-NI) and N omega-nitro-L-arginine methyl ester (L-NAME) produced PCP-like discriminative stimulus effects. 7-NI (17.8 mg/kg, i.m.) completely generalized to PCP. L-NAME (320-1000 mg/kg) produced partial generalization to PCP. D-NAME, the enantiomer of L-NAME, did not produce PCP-appropriate behavior. L-NAME was approximately 200-times more potent i.c.v., but did not fully generalize to PCP. Both NOS inhibitors were effective in producing catalepsy, which is an effect commonly produced by competitive and uncompetitive NMDA antagonists. 7-NI (32 mg/kg) produced catalepsy in all subjects, whereas L-NAME (3200 mg/kg) produced catalepsy in 50% of the subjects, D-NAME did not produce catalepsy. Pretreatment with L-arginine (32-3200 mg/kg) prevented the PCP-like discriminative stimulus and cataleptic effects of 7-NI (17.8-32 mg/kg), demonstrating that 7-NI produced PCP-like effects through blockade of NO synthesis. The current studies reveal that NOS inhibitors induced two behavioral actions, discriminative stimulus effects and catalepsy, that are very selective for NMDA antagonists in pigeons.
Jewett
D C
DC
Department of Pharmacology, University of Michigan Medical School, Ann Arbor 48109-0632, USA.
Butelman
E R
ER
Woods
J H
JH
D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D002375:Catalepsy / Q000139:chemically induced / Q000523:psychology; D010856:Columbidae; D003216:Conditioning, Operant / Q000187:drug effects; D004193:Discrimination Learning / Q000187:drug effects; D004192:Discrimination, Psychological / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000008:administration & dosage / Q000494:pharmacology*; D018691:Excitatory Amino Acid Antagonists / Q000008:administration & dosage / Q000494:pharmacology*; D007191:Indazoles / Q000008:administration & dosage / Q000494:pharmacology; D007273:Injections, Intramuscular; D007276:Injections, Intraventricular; D019331:NG-Nitroarginine Methyl Ester / Q000008:administration & dosage / Q000494:pharmacology; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors*; D010622:Phencyclidine / Q000008:administration & dosage / Q000494:pharmacology*
D004791:Enzyme Inhibitors; D018691:Excitatory Amino Acid Antagonists; D007191:Indazoles; D019001:Nitric Oxide Synthase; D010622:Phencyclidine; C080122:7-nitroindazole; D019331:NG-Nitroarginine Methyl Ester