title: Ethanol-induced sensitization depends preferentially on D1 rather than D2 dopamine receptors.
abstract: Behavioral sensitization, defined as a progressive increase in the locomotor stimulant effects elicited by repeated exposure to drugs of abuse, has been used as an animal model for drug craving in humans. The mesoaccumbens dopaminergic system has been proposed to be critically involved in this phenomenon; however, few studies have been designed to systematically investigate the effects of dopaminergic antagonists on development and expression of behavioral sensitization to ethanol in Swiss mice. We first tested the effects of D(1) antagonist SCH-23390 (0-0.03 mg/kg) or D(2) antagonist Sulpiride (0-30 mg/kg) on the locomotor responses to an acute injection of ethanol (2.0 g/kg). Results showed that all tested doses of the antagonists were effective in blocking ethanol's stimulant effects. In another set of experiments, mice were pretreated intraperitoneally with SCH-23390 (0.01 mg/kg) or Sulpiride (10 mg/kg) 30 min before saline or ethanol injection, for 21 days. Locomotor activity was measured weekly for 20 min. Four days following this pretreatment, all mice were challenged with ethanol. Both antagonists attenuated the development of ethanol sensitization, but only SCH-23390 blocked the expression of ethanol sensitization according to this protocol. When we tested a single dose (30 min before tests) of either antagonist in mice treated chronically with ethanol, both antagonists attenuated ethanol-induced effects. The present findings demonstrate that the concomitant administration of ethanol with D(1) but not D(2) antagonist prevented the expression of ethanol sensitization, suggesting that the neuroadaptations underlying ethanol behavioral sensitization depend preferentially on D(1) receptor actions.
authors.affiliation: Departamento de Farmacologia, Instituto de Ciências Biomédicas, Universidade de São Paulo, Brazil. camarini@icb.usp.br
authors.forename: Rosana
authors.initials: R
authors.lastname: Camarini
authors.forename: Tânia
authors.initials: T
authors.lastname: Marcourakis
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Teodorov
authors.forename: Mauricio
authors.initials: M
authors.lastname: Yonamine
authors.forename: Helena Maria
authors.initials: HM
authors.lastname: Calil
mesh_terms: D000818:Animals; D016739:Behavior, Addictive / Q000209:etiology / Q000503:physiopathology; D001522:Behavior, Animal / Q000187:drug effects* / Q000502:physiology*; D001552:Benzazepines / Q000494:pharmacology; D018492:Dopamine Antagonists / Q000494:pharmacology; D000431:Ethanol / Q000008:administration & dosage* / Q000097:blood; D006801:Humans; D008297:Male; D051379:Mice; D023421:Models, Animal; D009043:Motor Activity / Q000187:drug effects / Q000502:physiology; D017447:Receptors, Dopamine D1 / Q000187:drug effects* / Q000502:physiology*; D017448:Receptors, Dopamine D2 / Q000187:drug effects* / Q000502:physiology*; D013469:Sulpiride / Q000494:pharmacology
chemical_list: D001552:Benzazepines; D018492:Dopamine Antagonists; D017447:Receptors, Dopamine D1; D017448:Receptors, Dopamine D2; C534628:SCH 23390; D000431:Ethanol; D013469:Sulpiride