title: Habituation to test procedure modulates the involvement of dopamine D2- but not D1-receptors in ethanol-induced locomotor stimulation in mice.
abstract: BACKGROUND
  Novelty associated with behavioral testing has been shown to enhance psychostimulant- and morphine-induced locomotor stimulation. Evidence has demonstrated that novelty increases dopamine (DA) activity, and habituation to a novel environment reduces such activation. However, it is not clear whether novelty modulates ethanol-induced behavioral stimulation and whether DA plays a role in this effect.
  
  
  OBJECTIVE
  The present work sought to demonstrate a role of habituation to test procedure as a factor that could modulate the involvement of DA in ethanol-induced locomotor stimulation.
  
  
  METHODS
  Non-habituated (NH) and habituated (H) Swiss mice pretreated with DA D1- (SCH23390; 0-0.045 mg/kg) or D2-receptor (sulpiride; 0-50 mg/kg) antagonists were tested for ethanol (0-2.5 g/kg)-induced locomotor stimulation. Experiments with amphetamine (0-4 mg/kg), morphine (0-5 mg/kg) and caffeine (0-15 mg/kg)were designed to compare their results to those obtained with ethanol. The effect of the non-selective opioid receptor antagonist naltrexone (0-1.5 mg/kg) was also tested on ethanol-induced locomotor stimulation.
  
  
  RESULTS
  NH and H animals did not differ in their locomotor response to ethanol or caffeine; however, amphetamine- and morphine-induced stimulation was greater in NH than in H mice. SCH23390 only reduced ethanol-induced stimulation at doses that also reduced spontaneous activity in both NH and H mice. Sulpiride decreased ethanol-stimulated behavior only in the NH condition. Habituation did not modify the effect of sulpiride on amphetamine-, morphine- or caffeine-induced activation. Naltrexone (0-1.5 mg/kg) reduced ethanol-induced stimulation regardless of habituation.
  
  
  CONCLUSIONS
  The present data suggest that the participation of DA D2-receptors in ethanol-induced behavioral stimulation requires the presence of novelty. Results also support the involvement of neurotransmitter systems other than DA (i.e., endogenous opioid system) as important substrates mediating ethanol-induced locomotor activation.
authors.affiliation: Area de Psicobiología, Universtitat Jaume I. Campus de Riu Sec, Avda. Sos Baynat s/n, 12071 Castelló, Spain.
authors.forename: Raúl
authors.initials: R
authors.lastname: Pastor
authors.forename: Marta
authors.initials: M
authors.lastname: Miquel
authors.forename: Carlos M G
authors.initials: CM
authors.lastname: Aragon
mesh_terms: D000661:Amphetamine / Q000494:pharmacology; D000818:Animals; D001552:Benzazepines / Q000494:pharmacology; D002110:Caffeine / Q000494:pharmacology; D004777:Environment; D000431:Ethanol / Q000494:pharmacology*; D005106:Exploratory Behavior; D006185:Habituation, Psychophysiologic; D008297:Male; D051379:Mice; D009020:Morphine / Q000494:pharmacology; D009043:Motor Activity / Q000187:drug effects*; D009271:Naltrexone / Q000494:pharmacology; D017447:Receptors, Dopamine D1 / Q000502:physiology*; D017448:Receptors, Dopamine D2 / Q000502:physiology*; D013469:Sulpiride / Q000494:pharmacology; D001615:beta-Endorphin / Q000502:physiology
chemical_list: D001552:Benzazepines; D017447:Receptors, Dopamine D1; D017448:Receptors, Dopamine D2; D002110:Caffeine; D000431:Ethanol; D009271:Naltrexone; D001615:beta-Endorphin; D009020:Morphine; D013469:Sulpiride; D000661:Amphetamine