The effect of chronic treatment with clozapine and haloperidol on stimulus control by DOM.
The present study investigated the effects of chronic treatment with the atypical antipsychotic, clozapine, or the typical antipsychotic, haloperidol, on the stimulus properties of 2,5-dimethoxy-4-methylamphetamine ([-]-DOM) in rats trained to discriminate [-]-DOM (0.3 mg/kg; 75 min pre-treatment time) from vehicle. As compared with control values, treatment with clozapine (25 mg/kg.d) for 7 d caused a statistically significant 57% reduction in [-]-DOM-appropriate responding. Unlike clozapine, treatment with haloperidol (1 mg/kg.d) for 7 d did not affect the stimulus properties of [-]-DOM. These findings demonstrate that a functionally significant decrease in 5-HT2A receptor-mediated activity is a unique component of the in-vivo response to chronic treatment with clozapine but not haloperidol and, therefore, might account for some of the clinical differences associated with atypical antipsychotics.
Doat
Mireille M
MM
Department of Pharmacology and Toxicology, School of Medicine and Biomedical Sciences, State University of New York at Buffalo, NY 14214-3000, USA. doat@buffalo.edu
Rabin
Richard A
RA
Winter
Jerrold C
JC
D004290:DOM 2,5-Dimethoxy-4-Methylamphetamine / Q000494:pharmacology*; D000818:Animals; D014150:Antipsychotic Agents / Q000627:therapeutic use*; D001522:Behavior, Animal / Q000187:drug effects; D003024:Clozapine / Q000627:therapeutic use*; D004192:Discrimination, Psychological / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D006213:Hallucinogens / Q000494:pharmacology*; D006220:Haloperidol / Q000627:therapeutic use*; D008297:Male; D051381:Rats; D011916:Rats, Inbred F344; D044402:Receptor, Serotonin, 5-HT2A / Q000187:drug effects; D017366:Serotonin Receptor Agonists / Q000494:pharmacology
D014150:Antipsychotic Agents; D006213:Hallucinogens; D044402:Receptor, Serotonin, 5-HT2A; D017366:Serotonin Receptor Agonists; D004290:DOM 2,5-Dimethoxy-4-Methylamphetamine; D003024:Clozapine; D006220:Haloperidol