Effects of phencyclidine and other N-methyl-D-aspartate antagonists on the schedule-controlled behavior of rats. 1989

D J Sanger, and A Jackson
Synthelabo Recherche (L.E.R.S.), Bagneux, France.

The behavioral effects of phencyclidine (PCP) were compared with those of several compounds known to antagonize the actions of N-methyl-D-aspartate using two patterns of schedule-controlled responding in rats. Rates of variable interval responding suppressed by punishment were increased greatly by the benzodiazepine chlorodiazepoxide and showed small increases after MK-801 [(+)-5-methyl-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5,10-imine] . However, no consistent increases in response rates were produced by PCP, by the stereoisomers of N-allylnormetazocine (NANM: SKF 10,047) or by the anti-ischemic drug, ifenprodil. Small doses of PCP did increase rates of unpublished variable interval responding, as did a low dose of MK-801. Timing behavior maintained by a differential reinforcement of low rate schedule was disrupted by all the compounds studied. Response rates were increased by at least one dose of PCP, MK-801, (+)-NANM and 3-(2-carboxypiperazine-4-yl)propyl-1-phosphonic acid. The effect of MK-801, however, was considerably greater than that of the other compounds. Ifenprodil and (-)-NANM did not increase rates of responding but, at high doses, produced decreases in reinforcement frequency indicating that efficient timing behavior had been disrupted. These results show that although PCP, MK-801 and (+)-NANM produce generally similar behavioral effects, there may also be some differences between the compounds, notably a more consistent effect of MK-801 on punished responding. These behavioral effects may be related to antagonism of N-methyl-D-aspartate but ifenprodil, which is also an N-methyl-D-aspartate antagonist, does not show a similar behavioral profile.

UI MeSH Term Description Entries
D008297 Male Males
D010620 Phenazocine An opioid analgesic with actions and uses similar to MORPHINE. (From Martindale, The Extra Pharmacopoeia, 30th ed, p1095) Phenbenzorphan,Phenethylazocine,Narphen,Phenazocine Hydrobromide,Hydrobromide, Phenazocine
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
D010879 Piperazines Compounds that are derived from PIPERAZINE.
D010880 Piperidines A family of hexahydropyridines.
D011678 Punishment The application of an unpleasant stimulus or penalty for the purpose of eliminating or correcting undesirable behavior. Punishments
D011919 Rats, Inbred Strains Genetically identical individuals developed from brother and sister matings which have been carried out for twenty or more generations or by parent x offspring matings carried out with certain restrictions. This also includes animals with a long history of closed colony breeding. August Rats,Inbred Rat Strains,Inbred Strain of Rat,Inbred Strain of Rats,Inbred Strains of Rats,Rat, Inbred Strain,August Rat,Inbred Rat Strain,Inbred Strain Rat,Inbred Strain Rats,Inbred Strains Rat,Inbred Strains Rats,Rat Inbred Strain,Rat Inbred Strains,Rat Strain, Inbred,Rat Strains, Inbred,Rat, August,Rat, Inbred Strains,Rats Inbred Strain,Rats Inbred Strains,Rats, August,Rats, Inbred Strain,Strain Rat, Inbred,Strain Rats, Inbred,Strain, Inbred Rat,Strains, Inbred Rat
D012055 Reinforcement Schedule A schedule prescribing when the subject is to be reinforced or rewarded in terms of temporal interval in psychological experiments. The schedule may be continuous or intermittent. Reinforcement Schedules,Schedule, Reinforcement,Schedules, Reinforcement
D003213 Conditioning, Psychological Simple form of learning involving the formation, strengthening, or weakening of an association between a stimulus and a response. Conditioning, Psychology,Psychological Conditioning,Social Learning Theory,Social Learning Theories,Theory, Social Learning
D003986 Dibenzocycloheptenes A family of tricyclic hydrocarbons whose members include many of the commonly used tricyclic antidepressants (ANTIDEPRESSIVE AGENTS, TRICYCLIC).

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