Nitric oxide synthase inhibitors produce phencyclidine-like behavioral effects in pigeons. 1996

D C Jewett, and E R Butelman, and J H Woods
Department of Pharmacology, University of Michigan Medical School, Ann Arbor 48109-0632, USA.

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.

UI MeSH Term Description Entries
D007191 Indazoles A group of heterocyclic aromatic organic compounds consisting of the fusion of BENZENE and PYRAZOLES. Indazole
D007273 Injections, Intramuscular Forceful administration into a muscle of liquid medication, nutrient, or other fluid through a hollow needle piercing the muscle and any tissue covering it. Intramuscular Injections,Injection, Intramuscular,Intramuscular Injection
D007276 Injections, Intraventricular Injections into the cerebral ventricles. Intraventricular Injections,Injection, Intraventricular,Intraventricular Injection
D010622 Phencyclidine A hallucinogen formerly used as a veterinary anesthetic, and briefly as a general anesthetic for humans. Phencyclidine is similar to KETAMINE in structure and in many of its effects. Like ketamine, it can produce a dissociative state. It exerts its pharmacological action through inhibition of NMDA receptors (RECEPTORS, N-METHYL-D-ASPARTATE). As a drug of abuse, it is known as PCP and Angel Dust. 1-(1-Phenylcyclohexyl)piperidine,Angel Dust,CL-395,GP-121,Phencyclidine Hydrobromide,Phencyclidine Hydrochloride,Sernyl,Serylan,CL 395,CL395,Dust, Angel,GP 121,GP121
D010856 Columbidae Family in the order COLUMBIFORMES, comprised of pigeons or doves. They are BIRDS with short legs, stout bodies, small heads, and slender bills. Some sources call the smaller species doves and the larger pigeons, but the names are interchangeable. Columba livia,Doves,Pigeons,Domestic Pigeons,Feral Pigeons,Rock Doves,Rock Pigeons,Domestic Pigeon,Dove,Dove, Rock,Doves, Rock,Feral Pigeon,Pigeon,Pigeon, Domestic,Pigeon, Feral,Pigeon, Rock,Pigeons, Domestic,Pigeons, Feral,Pigeons, Rock,Rock Dove,Rock Pigeon
D002375 Catalepsy A condition characterized by inactivity, decreased responsiveness to stimuli, and a tendency to maintain an immobile posture. The limbs tend to remain in whatever position they are placed (waxy flexibility). Catalepsy may be associated with PSYCHOTIC DISORDERS (e.g., SCHIZOPHRENIA, CATATONIC), nervous system drug toxicity, and other conditions. Cerea Flexibilitas,Flexibility, Waxy,Anochlesia,Anochlesias,Catalepsies,Flexibilitas, Cerea,Flexibilities, Waxy,Waxy Flexibilities,Waxy Flexibility
D003216 Conditioning, Operant Learning situations in which the sequence responses of the subject are instrumental in producing reinforcement. When the correct response occurs, which involves the selection from among a repertoire of responses, the subject is immediately reinforced. Instrumental Learning,Learning, Instrumental,Operant Conditioning,Conditionings, Operant,Instrumental Learnings,Learnings, Instrumental,Operant Conditionings
D004192 Discrimination, Psychological Differential response to different stimuli. Discrimination, Psychology,Psychological Discrimination
D004193 Discrimination Learning Learning that is manifested in the ability to respond differentially to various stimuli. Discriminative Learning,Discrimination Learnings,Discriminative Learnings,Learning, Discrimination,Learning, Discriminative
D004305 Dose-Response Relationship, Drug The relationship between the dose of an administered drug and the response of the organism to the drug. Dose Response Relationship, Drug,Dose-Response Relationships, Drug,Drug Dose-Response Relationship,Drug Dose-Response Relationships,Relationship, Drug Dose-Response,Relationships, Drug Dose-Response

Related Publications

D C Jewett, and E R Butelman, and J H Woods
July 1994, Endocrinology,
D C Jewett, and E R Butelman, and J H Woods
July 1998, Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology,
D C Jewett, and E R Butelman, and J H Woods
April 2003, Neuropharmacology,
D C Jewett, and E R Butelman, and J H Woods
January 2000, Methods in molecular medicine,
D C Jewett, and E R Butelman, and J H Woods
February 1995, European journal of pharmacology,
D C Jewett, and E R Butelman, and J H Woods
December 1996, The Journal of investigative dermatology,
D C Jewett, and E R Butelman, and J H Woods
May 2001, Psychopharmacology,
D C Jewett, and E R Butelman, and J H Woods
February 1999, European journal of pharmacology,
D C Jewett, and E R Butelman, and J H Woods
September 1997, Acta anaesthesiologica Sinica,
D C Jewett, and E R Butelman, and J H Woods
January 1997, Brain research,
Copied contents to your clipboard!