Conditioned taste aversions induced by phencyclidine and other antagonists of N-methyl-D-aspartate.
Taste aversions can be conditioned in rats by a variety of psychoactive drugs, including those with reinforcing properties. Previous research, however, has not established clearly whether phencyclidine and related drugs are active in such procedures. The present study was carried out to investigate whether phencyclidine would induce a conditioned taste aversion and whether several other compounds (MK-801, the stereoisomers of NANM and ifenprodil) which, like phencyclidine, are known to antagonise the actions of N-methyl-D-aspartate (NMDA), would produce similar effects. When rats received injections of these compounds, after consuming a novel solution of saccharin, their subsequent consumption of the same solution decreased. The smallest doses of the different drugs which induced clear taste aversions were: phencyclidine 3 mg/kg, MK-801 0.3 mg/kg, (+)-NANM 10 mg/kg, (-)-NANM 3 mg/kg and ifenprodil 10 mg/kg. Thus, all the drugs were active. However, as neither the potencies nor the efficacies of the different compounds in inducing taste aversions correlated with their other behavioural effects or with their relative potencies in antagonising the effects of NMDA or in displacing phencyclidine from its binding sites, the mechanisms involved are unclear.
Jackson
A
A
Laboratoires d'Etudes et de Recherches Synthélabo, Bagneux, France.
Sanger
D J
DJ
D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000818:Animals; D001224:Aspartic Acid / Q000031:analogs & derivatives* / Q000037:antagonists & inhibitors; D001362:Avoidance Learning / Q000187:drug effects*; D003216:Conditioning, Operant / Q000187:drug effects*; D008297:Male; D016202:N-Methylaspartate; D010620:Phenazocine / Q000031:analogs & derivatives / Q000494:pharmacology; D010622:Phencyclidine / Q000494:pharmacology*; D010880:Piperidines / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D013649:Taste / Q000187:drug effects*
D000317:Adrenergic alpha-Antagonists; D010880:Piperidines; D001224:Aspartic Acid; D016202:N-Methylaspartate; C012134:SK&F 10047; D010620:Phenazocine; D010622:Phencyclidine; C010739:ifenprodil