title: The effect of quetiapine (Seroquel™) on conditioned place preference and elevated plus maze tests in rats when administered alone and in combination with (+)-amphetamine.
abstract: BACKGROUND
  Recent case reports describe recreational use of quetiapine and drug-seeking behaviour to obtain quetiapine, an atypical antipsychotic.
  
  
  OBJECTIVE
  We examined the hypothesis that quetiapine (10, 20 or 40 mg/kg) alone or co-administered with (+)-amphetamine (0.25, 0.5, 0.75 or 2.0 mg/kg) will affect reward and/or decrease anxiety in rats, as measured by conditioned place preference (CPP) and elevated plus maze (EPM) test, respectively.
  
  
  RESULTS
  Quetiapine (20 mg/kg) produced greater open arm time and entries in the EPM test compared to 10 and 40 mg/kg, and quetiapine (10 mg/kg) significantly increased open arm entries and time when co-administered with (+)-amphetamine (0.5 mg/kg) compared to (+)-amphetamine (0.5 mg/kg) alone, suggesting decreased anxiety. Quetiapine (10, 20 or 40 mg/kg) produced no CPP when administered alone; the lowest dose of quetiapine (10 mg/kg) reduced CPP produced by a low dose of (+)-amphetamine (0.25 mg/kg), but had no significant effect on CPP produced by a higher dose (0.5 mg/kg).
  
  
  CONCLUSIONS
  The quetiapine-induced anxiolytic effect in the EPM might explain why humans are misusing quetiapine and combining it with (+)-amphetamine. It is possible that humans experience an anxiolytic effect of the combined drugs and relatively unaltered rewarding effects of (+)-amphetamine. The results shed some light on the question of why humans are abusing and misusing quetiapine, despite its dopamine (DA) D2 receptor antagonism; it will be the task of future studies to identify the pharmacological mechanism mediating this behaviour.
authors.affiliation: Department of Psychology, Queen's University, Kingston, Ontario, Canada, K7L 3N6.
authors.forename: Angela E
authors.initials: AE
authors.lastname: McLelland
authors.forename: Mathew T
authors.initials: MT
authors.lastname: Martin-Iverson
authors.forename: Richard J
authors.initials: RJ
authors.lastname: Beninger
mesh_terms: D000661:Amphetamine / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D014150:Antipsychotic Agents / Q000008:administration & dosage / Q000494:pharmacology*; D001007:Anxiety; D001522:Behavior, Animal / Q000187:drug effects*; D000697:Central Nervous System Stimulants / Q000008:administration & dosage / Q000494:pharmacology*; D003213:Conditioning, Psychological / Q000187:drug effects; D003987:Dibenzothiazepines / Q000008:administration & dosage / Q000494:pharmacology*; D004357:Drug Synergism; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D000069348:Quetiapine Fumarate; D051381:Rats; D017208:Rats, Wistar; D012201:Reward
chemical_list: D014150:Antipsychotic Agents; D000697:Central Nervous System Stimulants; D003987:Dibenzothiazepines; D000069348:Quetiapine Fumarate; D000661:Amphetamine