title: Chronic treatment with aripiprazole prevents development of dopamine supersensitivity and potentially supersensitivity psychosis.
abstract: BACKGROUND
  Long-term treatment of schizophrenia with antipsychotics is crucial for relapse prevention, but a prolonged blockade of D(2) dopamine receptors may lead to the development of supersensitivity psychosis. We investigated the chronic effects of aripiprazole (ARI) on dopamine sensitivity.
  
  
  METHODS
  We administered ARI (1.5 mg/kg/d), haloperidol (HAL; 0.75 mg/kg/d), or vehicle (VEH) via minipump for 14 days to drug-naive rats or to rats pretreated with HAL (0.75 mg/kg/d) or VEH via minipump for 14 days. On the seventh day following treatment cessation, we examined the effects of the treatment conditions on the locomotor response to methamphetamine and on striatal D(2) receptor density (N = 4-10/condition/experiment).
  
  
  RESULTS
  Chronic treatment with HAL led to significant increases in locomotor response and D(2) receptor density, compared with the effects of chronic treatment with either VEH or ARI; there were no significant differences in either locomotor response or D(2) density between the VEH- and ARI-treated groups. We also investigated the effects of chronic treatment with HAL, ARI, or VEH preceded by HAL or VEH treatment on locomotor response and D(2) density. ANOVA analysis indicated that the rank ordering of groups for both locomotor response and D(2) density was HAL-HAL > HAL-VEH > HAL-ARI > VEH-VEH.
  
  
  CONCLUSIONS
  Chronic treatment with ARI prevents development of dopamine supersensitivity and potentially supersensitivity psychosis, suggesting that by reducing excessive sensitivity to dopamine and by stabilizing sensitivity for an extended period of time, ARI may be helpful for some patients with treatment-resistant schizophrenia.
authors.affiliation: Department of Psychiatry, Chiba University Graduate School of Medicine, Chiba, Japan. tadokoroshigenori@gmail.com
authors.forename: Shigenori
authors.initials: S
authors.lastname: Tadokoro
authors.forename: Naoe
authors.initials: N
authors.lastname: Okamura
authors.forename: Yoshimoto
authors.initials: Y
authors.lastname: Sekine
authors.forename: Nobuhisa
authors.initials: N
authors.lastname: Kanahara
authors.forename: Kenji
authors.initials: K
authors.lastname: Hashimoto
authors.forename: Masaomi
authors.initials: M
authors.lastname: Iyo
mesh_terms: D000818:Animals; D014150:Antipsychotic Agents / Q000494:pharmacology*; D000068180:Aripiprazole; D003342:Corpus Striatum / Q000187:drug effects; D065127:Dopamine D2 Receptor Antagonists; D018765:Dopamine Uptake Inhibitors; D006220:Haloperidol / Q000494:pharmacology*; D008134:Long-Term Care; D008297:Male; D008694:Methamphetamine; D009043:Motor Activity / Q000187:drug effects; D010879:Piperazines / Q000494:pharmacology*; D011605:Psychoses, Substance-Induced / Q000503:physiopathology*; D015363:Quinolones / Q000494:pharmacology*; D011869:Radioligand Assay; D051381:Rats; D017207:Rats, Sprague-Dawley; D017448:Receptors, Dopamine D2 / Q000187:drug effects*; D012559:Schizophrenia / Q000503:physiopathology*
chemical_list: D014150:Antipsychotic Agents; D065127:Dopamine D2 Receptor Antagonists; D018765:Dopamine Uptake Inhibitors; D010879:Piperazines; D015363:Quinolones; D017448:Receptors, Dopamine D2; D008694:Methamphetamine; D000068180:Aripiprazole; D006220:Haloperidol