title: Effects of rimonabant on the development of single dose-induced behavioral sensitization to ethanol, morphine and cocaine in mice.
abstract: BACKGROUND
  The endocannabinoid system has been implicated in the neurobiological mechanism underlying drug addiction, especially the primary rewarding dopamine-dependent processes. Therefore, endocannabinoid receptor antagonists, such as the CB1 cannabinoid antagonist rimonabant, have been proposed as candidates for preventive addiction therapies.
  
  
  OBJECTIVE
  Investigate the possible involvement of CB1 receptors in the development of behavioral sensitization to ethanol, morphine and cocaine in mice.
  
  
  METHODS
  We compared the effects of different doses of rimonabant (0.3, 1, 3 and 10mg/kg) on spontaneous locomotor activity in the open-field, hyperlocomotion induced by acute administration of ethanol (1.8g/kg), morphine (20mg/kg) or cocaine (10mg/kg) and on subsequent drug-induced locomotor sensitization using a two-injection protocol in mice. We also investigated a possible depressive-like effect of an acute rimonabant challenge at the highest dose and its potential anxiogenic property.
  
  
  RESULTS
  At the highest dose, rimonabant abolished ethanol- and cocaine-induced hyperlocomotion and behavioral sensitization without modifying spontaneous and central locomotor activity or inducing depressive-like behavior on the forced swim test in mice. The other doses of rimonabant also selectively blocked acute ethanol-induced central hyperlocomotion. Although rimonabant at 0.3 and 1mg/kg potentiated the central hyperlocomotion induced by acute morphine injection, it was effective in attenuating morphine-induced behavioral sensitization at all doses.
  
  
  CONCLUSIONS
  Because the neural basis of behavioral sensitization has been proposed to correspond to some components of addiction, our findings indicate that the endocannabinoid system might be involved in ethanol, cocaine and morphine abuse.
authors.affiliation: Departamento de Ciências da Saúde, Universidade Estadual de Santa Cruz - UESC, Ilhéus, BA, Brazil. Electronic address: edumarinho@hotmail.com.
authors.forename: Eduardo A V
authors.initials: EA
authors.lastname: Marinho
authors.affiliation: Departamento de Ciências da Saúde, Universidade Estadual de Santa Cruz - UESC, Ilhéus, BA, Brazil.
authors.forename: Alexandre J
authors.initials: AJ
authors.lastname: Oliveira-Lima
authors.affiliation: Departamento de Fisiologia, Universidade Federal de São Paulo - UNIFESP, São Paulo, SP, Brazil.
authors.forename: Renan
authors.initials: R
authors.lastname: Santos
authors.affiliation: Departamento de Fisiologia, Universidade Federal de São Paulo - UNIFESP, São Paulo, SP, Brazil.
authors.forename: André W
authors.initials: AW
authors.lastname: Hollais
authors.affiliation: Departamento de Farmacologia, Universidade Federal de São Paulo - UNIFESP, São Paulo, SP, Brazil.
authors.forename: Marilia A
authors.initials: MA
authors.lastname: Baldaia
authors.affiliation: Departamento de Fisiologia, Universidade Federal de São Paulo - UNIFESP, São Paulo, SP, Brazil.
authors.forename: Raphael
authors.initials: R
authors.lastname: Wuo-Silva
authors.affiliation: Departamento de Fisiologia, Universidade Federal de São Paulo - UNIFESP, São Paulo, SP, Brazil.
authors.forename: Thais S
authors.initials: TS
authors.lastname: Yokoyama
authors.affiliation: Departamento de Psicobiologia, Universidade Federal de São Paulo - UNIFESP, São Paulo, SP, Brazil.
authors.forename: André L
authors.initials: AL
authors.lastname: Takatsu-Coleman
authors.affiliation: Departamento de Farmacologia, Universidade Federal de São Paulo - UNIFESP, São Paulo, SP, Brazil.
authors.forename: Camilla L
authors.initials: CL
authors.lastname: Patti
authors.affiliation: Departamento de Fisiologia, Universidade Federal de São Paulo - UNIFESP, São Paulo, SP, Brazil; Departamento de Farmacologia, Universidade Federal de São Paulo - UNIFESP, São Paulo, SP, Brazil.
authors.forename: Beatriz M
authors.initials: BM
authors.lastname: Longo
authors.affiliation: Departamento de Psicobiologia, Universidade Federal de São Paulo - UNIFESP, São Paulo, SP, Brazil. Electronic address: berro.lf@gmail.com.
authors.forename: Laís F
authors.initials: LF
authors.lastname: Berro
authors.affiliation: Departamento de Farmacologia, Universidade Federal de São Paulo - UNIFESP, São Paulo, SP, Brazil; Departamento de Psicobiologia, Universidade Federal de São Paulo - UNIFESP, São Paulo, SP, Brazil.
authors.forename: Roberto
authors.initials: R
authors.lastname: Frussa-Filho
mesh_terms: D017109:Akathisia, Drug-Induced / Q000378:metabolism / Q000517:prevention & control*; D000818:Animals; D021461:Animals, Outbred Strains; D001007:Anxiety / Q000139:chemically induced; D063387:Cannabinoid Receptor Antagonists / Q000494:pharmacology*; D002492:Central Nervous System Depressants / Q000494:pharmacology; D003042:Cocaine / Q000494:pharmacology; D003863:Depression / Q000139:chemically induced; D018765:Dopamine Uptake Inhibitors / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D000431:Ethanol / Q000494:pharmacology; D008297:Male; D051379:Mice; D009020:Morphine / Q000494:pharmacology; D009043:Motor Activity / Q000187:drug effects / Q000502:physiology; D009294:Narcotics / Q000494:pharmacology; D010880:Piperidines / Q000494:pharmacology*; D011720:Pyrazoles / Q000494:pharmacology*; D043884:Receptor, Cannabinoid, CB1 / Q000037:antagonists & inhibitors / Q000378:metabolism; D000077285:Rimonabant; D019966:Substance-Related Disorders / Q000378:metabolism / Q000517:prevention & control
chemical_list: D063387:Cannabinoid Receptor Antagonists; D002492:Central Nervous System Depressants; D018765:Dopamine Uptake Inhibitors; D009294:Narcotics; D010880:Piperidines; D011720:Pyrazoles; D043884:Receptor, Cannabinoid, CB1; D000431:Ethanol; D009020:Morphine; D003042:Cocaine; D000077285:Rimonabant
keywords: Behavioral sensitization; Cocaine; Ethanol; Morphine; Rimonabant