title: Acute quetiapine dose-dependently exacerbates anhedonia induced by withdrawal from escalating doses of d-amphetamine.
abstract: Recent clinical studies show that the atypical antipsychotic medication, quetiapine, may be beneficial in the treatment of substance abuse by alleviating the withdrawal-negative affect stage of addiction. Since the effect of quetiapine on central reward function is largely unknown we studied its effects on brain stimulation reward in animals under withdrawal from escalating doses of d-amphetamine. Male Sprague-Dawley rats were trained to produce an operant response to receive a short train of electrical stimulation to the lateral hypothalamus. Measures of reward threshold were determined with the curve-shift method in different groups of rats before, and during four days after treatment with escalating doses (1 to 10mg/kg, i.p.) of d-amphetamine or its vehicle. At 24h of withdrawal, the effects of two doses of quetiapine (2 and 10mg/kg i.p.) were tested. Animals treated with d-amphetamine showed a 25% reward deficit at 24h of withdrawal, an effect that decreased progressively over the next three days. Quetiapine attenuated reward in the vehicle-control animals, and amplified the anhedonia at the moderate, but not the low, dose in the animals under withdrawal. These results show that acute treatment with clinically relevant doses of quetiapine for the treatment of schizophrenia may exacerbate anhedonia induced by amphetamine withdrawal. Further research should investigate whether repeated treatment with quetiapine has the ability to reverse amphetamine withdrawal-induced anhedonia.
authors.affiliation: Centre de Recherche Fernand-Seguin, Hôpital Louis-H. Lafontaine et Département de Psychiatrie, Université de Montréal, Montréal, Québec, Canada H1N 3V2.
authors.forename: Simon
authors.initials: S
authors.lastname: Zhornitsky
authors.forename: Stéphane
authors.initials: S
authors.lastname: Potvin
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Stip
authors.forename: Pierre-Paul
authors.initials: PP
authors.lastname: Rompré
mesh_terms: D019969:Amphetamine-Related Disorders / Q000188:drug therapy; D000818:Animals; D014150:Antipsychotic Agents / Q000008:administration & dosage / Q000009:adverse effects*; D001522:Behavior, Animal / Q000187:drug effects; D000697:Central Nervous System Stimulants / Q000008:administration & dosage / Q000009:adverse effects*; D003913:Dextroamphetamine / Q000008:administration & dosage / Q000009:adverse effects*; D003987:Dibenzothiazepines / Q000008:administration & dosage / Q000009:adverse effects*; D004305:Dose-Response Relationship, Drug; D004361:Drug Tolerance; D004558:Electric Stimulation; D007031:Hypothalamus / Q000502:physiology / Q000601:surgery; D008297:Male; D057181:Pleasure / Q000187:drug effects*; D000069348:Quetiapine Fumarate; D051381:Rats; D017207:Rats, Sprague-Dawley; D012201:Reward; D012559:Schizophrenia / Q000188:drug therapy; D013375:Substance Withdrawal Syndrome / Q000188:drug therapy / Q000503:physiopathology / Q000523:psychology*
chemical_list: D014150:Antipsychotic Agents; D000697:Central Nervous System Stimulants; D003987:Dibenzothiazepines; D000069348:Quetiapine Fumarate; D003913:Dextroamphetamine