title: Residual dopamine receptor desensitization following either high- or low-dose sub-chronic prior exposure to the atypical anti-psychotic drug olanzapine.
abstract: BACKGROUND
  Anti-psychotic drugs are antagonists of dopamine D2 receptors and repeated administration may lead to the development of dopamine receptor supersensitivity.
  
  
  OBJECTIVE
  The objective of this study is to investigate the effects of sub-chronic olanzapine treatments upon the induction of dopamine receptor supersensitivity.
  
  
  METHODS
  Rats were administered ten daily low or high doses of the atypical anti-psychotic drug olanzapine (0.01 or 1.0 mg/kg). After 5 days of withdrawal, all groups received 2.0 mg/kg apomorphine on five successive days. Five days after the apomorphine sensitization protocol, in separate experiments, either a conditioning test or an apomorphine sensitization test was conducted.
  
  
  RESULTS
  During the anti-psychotic treatment the high dose of olanzapine induced profound locomotion suppression, whereas the low dose had no effect upon locomotion. The apomorphine treatments given to the vehicle control group generated locomotor sensitization. This sensitization effect was attenuated by the same degree for both the low or high dose prior olanzapine treatments. Also, the low and high-dose olanzapine pre-treatments diminished subsequent apomorphine-conditioned and apomorphine-sensitized locomotor responses.
  
  
  CONCLUSIONS
  The equivalent attenuation of the apomorphine sensitization produced by both olanzapine doses indicates that this effect was unrelated to the direct effects of olanzapine upon locomotion. Furthermore, the persistence of the desensitization effects well after the termination of the olanzapine treatments is indicative of a residual desensitization of the dopamine system. These findings are of importance when considering the use of atypical anti-psychotic drugs in the treatment of psychoses and other disorders in which overactivity of the dopamine system is considered a contributory factor.
authors: Behavioral Pharmacology Group, Laboratory of Animal Morphology and Pathology, State University of North Fluminense Darcy Ribeiro, Avenida Alberto Lamego, 2000, Campos dos Goytacazes, 28013-602 Rio de Janeiro, Brazil.
authors: Flávia Regina Cruz
authors: FR
authors: Dias
authors: Liana Wermelinger
authors: LW
authors: de Matos
authors: Maria de Fátima
authors: Mde F
authors: Dos Santos Sampaio
authors: Robert J
authors: RJ
authors: Carey
authors: Marinete Pinheiro
authors: MP
authors: Carrera
mesh_terms: D000818:Animals; D014150:Antipsychotic Agents / Q000008:administration & dosage / Q000494:pharmacology*; D001058:Apomorphine / Q000494:pharmacology*; D001569:Benzodiazepines / Q000008:administration & dosage / Q000494:pharmacology*; D003213:Conditioning, Psychological / Q000187:drug effects; D018491:Dopamine Agonists / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D008297:Male; D009043:Motor Activity / Q000187:drug effects; D000077152:Olanzapine; D051381:Rats; D017208:Rats, Wistar; D017448:Receptors, Dopamine D2 / Q000187:drug effects* / Q000378:metabolism
chemical_list: D014150:Antipsychotic Agents; D018491:Dopamine Agonists; D017448:Receptors, Dopamine D2; D001569:Benzodiazepines; D001058:Apomorphine; D000077152:Olanzapine