RATIONALE: A cannabinoid hypothesis of schizophrenia has been proposed according to which cognitive dysfunction could be associated with dysregulation of an endogenous cannabinoid system. OBJECTIVE: The present study investigated whether SR 141716, a selective CB1 receptor antagonist, was able to reduce the hyperactivity induced in gerbils by various stimulant drugs known to produce or exacerbate schizophrenic symptoms. METHODS: Cocaine, d-amphetamine, morphine, and Win 55212-2 were administered intraperitoneally (IP) either immediately before placing the animals in the test apparatus (non-habituated gerbils) or after a 2- to 3-h habituation period in the actimeter (habituated gerbils). SR 141716 was given IP 30 min before the injection of stimulant drugs. Horizontal activity was recorded every 10 min for 1 h in Digiscan activity monitor. RESULTS: SR 141716 (0.3-3 mg/kg) dose-dependently suppressed the enhanced locomotor activity induced by each stimulant drug in habituated gerbils, but not in non-habituated animals. Clozapine, an atypical antipsychotic compound, but not haloperidol, shared with SR 141716, the ability to differentially affect drug-induced hyperactivity in habituated versus non-habituated gerbils. CONCLUSION: The activation of cannabinoid systems is a required, permissive element in the ability of cocaine, d-amphetamine, morphine, and Win 55212-2 to reinstate behaviour, i.e., to override stimulus satiation.
RATIONALE: A cannabinoid hypothesis of schizophrenia has been proposed according to which cognitive dysfunction could be associated with dysregulation of an endogenous cannabinoid system. OBJECTIVE: The present study investigated whether SR 141716, a selective CB1 receptor antagonist, was able to reduce the hyperactivity induced in gerbils by various stimulant drugs known to produce or exacerbate schizophrenic symptoms. METHODS:Cocaine, d-amphetamine, morphine, and Win 55212-2 were administered intraperitoneally (IP) either immediately before placing the animals in the test apparatus (non-habituated gerbils) or after a 2- to 3-h habituation period in the actimeter (habituated gerbils). SR 141716 was given IP 30 min before the injection of stimulant drugs. Horizontal activity was recorded every 10 min for 1 h in Digiscan activity monitor. RESULTS:SR 141716 (0.3-3 mg/kg) dose-dependently suppressed the enhanced locomotor activity induced by each stimulant drug in habituated gerbils, but not in non-habituated animals. Clozapine, an atypical antipsychotic compound, but not haloperidol, shared with SR 141716, the ability to differentially affect drug-induced hyperactivity in habituated versus non-habituated gerbils. CONCLUSION: The activation of cannabinoid systems is a required, permissive element in the ability of cocaine, d-amphetamine, morphine, and Win 55212-2 to reinstate behaviour, i.e., to override stimulus satiation.
Authors: Eleni T Tzavara; Richard J Davis; Kenneth W Perry; Xia Li; Craig Salhoff; Frank P Bymaster; Jeffrey M Witkin; George G Nomikos Journal: Br J Pharmacol Date: 2003-02 Impact factor: 8.739
Authors: Mark D Black; Rachel J Stevens; Nancy Rogacki; Robert E Featherstone; Yaw Senyah; Odessa Giardino; Beth Borowsky; Jeanne Stemmelin; Caroline Cohen; Philippe Pichat; Michal Arad; Segev Barak; Amaya De Levie; Ina Weiner; Guy Griebel; Geoffrey B Varty Journal: Psychopharmacology (Berl) Date: 2010-12-22 Impact factor: 4.530
Authors: Pedro H Gobira; Ana C Oliveira; Julia S Gomes; Vivian T da Silveira; Laila Asth; Juliana R Bastos; Edleusa M Batista; Ana C Issy; Bright N Okine; Antonio C de Oliveira; Fabiola M Ribeiro; Elaine A Del Bel; Daniele C Aguiar; David P Finn; Fabricio A Moreira Journal: Br J Pharmacol Date: 2018-09-14 Impact factor: 8.739