Potentiation of DOM-induced stimulus control by non-competitive NMDA antagonists: a link between the glutamatergic and serotonergic hypotheses of schizophrenia.
The present investigation examined the interaction between 2,5-dimethoxy-4-methylamphetamine [DOM] and non-competitive NMDA antagonists in rats trained with DOM [0.6 mg/kg; 75 min pretreatment time] as a discriminative stimulus. Pretreatment with phencyclidine [PCP] at a dose of 3 mg/kg shifted the DOM dose-response relationship to the left. When a fixed dose of DOM [0.1 mg/kg] which by itself yielded 32% DOM-appropriate responding was combined with a range of doses of PCP, dizocilpine, and ketamine, DOM-appropriate percentages increased to maxima of 73%, 84%, and 79%, respectively. When given alone, PCP, dizocilpine, and ketamine were followed by maxima of 36%, 15%, and 13%, respectively. It is concluded that the effects of DOM as a discriminative stimulus are potentiated by pretreatment with non-competitive antagonists of glutamate receptors of the NMDA subtype. These data suggest that the application of the technique of drug-induced stimulus control may prove useful in the reconciliation and integration of current hypotheses as to the etiology of psychotic disorders.
Winter
J C
JC
Department of Pharmacology and Toxicology, School of Medicine and Biomedical Sciences, State University of New York at Buffalo, 14214-3000, USA. jcwinter@acsu.buffalo.edu
Doat
M
M
Rabin
R A
RA
D004290:DOM 2,5-Dimethoxy-4-Methylamphetamine / Q000494:pharmacology*; D000818:Animals; D004193:Discrimination Learning / Q000187:drug effects*; D004195:Disease Models, Animal; D016291:Dizocilpine Maleate / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology*; D006213:Hallucinogens / Q000494:pharmacology*; D007649:Ketamine / Q000494:pharmacology; D008297:Male; D016202:N-Methylaspartate / Q000037:antagonists & inhibitors; D010622:Phencyclidine / Q000494:pharmacology; D051381:Rats; D011916:Rats, Inbred F344; D012559:Schizophrenia / Q000209:etiology / Q000503:physiopathology
D018691:Excitatory Amino Acid Antagonists; D006213:Hallucinogens; D004290:DOM 2,5-Dimethoxy-4-Methylamphetamine; D016202:N-Methylaspartate; D007649:Ketamine; D016291:Dizocilpine Maleate; D010622:Phencyclidine