title: Role of D1-like receptors in amphetamine-induced behavioral sensitization: a study using D1A receptor knockout mice.
abstract: BACKGROUND
  The role played by D(1)-like receptors in amphetamine-induced behavioral sensitization has been examined using both the D(1)-like receptor antagonist, SCH 23390, and the D(1A) receptor knockout mouse (i.e. D(1A)-deficient mice). Studies using these two approaches have provided conflicting evidence about the importance of D(1)-like receptors for amphetamine-induced behavioral sensitization.
  
  
  OBJECTIVE
  The purpose of the present study was to determine: (a) whether D(1A)-deficient mice exhibit amphetamine-induced locomotor sensitization after 3 and 17 drug abstinence days, and (b) whether SCH 23390, which binds to both D(1A) and D(1B) receptor subtypes, blocks development of amphetamine sensitization in wild-type and D(1A)-deficient mice.
  
  
  METHODS
  In the first experiment, adult wild-type and D(1A)-deficient mice were injected with amphetamine (0, 1, 2, 4, or 8 mg/kg, IP) for 7 consecutive days. In the second experiment, wild-type and D(1A)-deficient mice were pretreated with SCH 23390 (0, 0.15, or 0.5 mg/kg, IP) 30 min prior to being injected with amphetamine (0 or 8 mg/kg, IP). After each daily amphetamine injection, mice were placed in activity chambers where distance traveled (i.e. horizontal locomotor activity) was measured for 60 min. On the test days, which occurred after 3 or 17 drug abstinence days, mice were injected with 1 mg/kg amphetamine and locomotion was measured for 120 min.
  
  
  RESULTS
  Both wild-type and D(1A)-deficient mice exhibited amphetamine-induced locomotor sensitization. Pretreatment with 0.5 mg/kg SCH 23390 blocked the development of locomotor sensitization in wild-type mice, but did not alter the sensitized responding of D(1A)-deficient mice.
  
  
  CONCLUSIONS
  It appears that D(1)-like receptors are necessary for the development of amphetamine sensitization in wild-type mice, while neither the D(1A) nor D(1B) receptor subtypes are necessary for the amphetamine-induced locomotor sensitization of D(1A)-deficient mice. A possible explanation for these conflicting results is that D(1A)-deficient mice may have a compensatory mechanism (not involving D(1B) receptors) that allows them to exhibit amphetamine-induced behavioral sensitization in the absence of the D(1A) receptor.
authors.affiliation: Department of Psychology, California State University, San Bernadino, 92407, USA.
authors.forename: Patrick E
authors.initials: PE
authors.lastname: Karper
authors.forename: Herminia
authors.initials: H
authors.lastname: De la Rosa
authors.forename: Eva R
authors.initials: ER
authors.lastname: Newman
authors.forename: Catherine M
authors.initials: CM
authors.lastname: Krall
authors.forename: Arbi
authors.initials: A
authors.lastname: Nazarian
authors.forename: Sanders A
authors.initials: SA
authors.lastname: McDougall
authors.forename: Cynthia A
authors.initials: CA
authors.lastname: Crawford
mesh_terms: D000661:Amphetamine / Q000494:pharmacology*; D000818:Animals; D001552:Benzazepines / Q000494:pharmacology; D015259:Dopamine Agents / Q000494:pharmacology*; D018492:Dopamine Antagonists / Q000494:pharmacology; D005260:Female; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009043:Motor Activity / Q000187:drug effects* / Q000502:physiology; D017447:Receptors, Dopamine D1 / Q000037:antagonists & inhibitors / Q000172:deficiency* / Q000235:genetics / Q000502:physiology
chemical_list: D001552:Benzazepines; D015259:Dopamine Agents; D018492:Dopamine Antagonists; D017447:Receptors, Dopamine D1; C098593:dopamine D1A receptor; D000661:Amphetamine