Clara Touriño1, Rafael Maldonado, Olga Valverde. 1. Grup de Recerca de Neurobiologia del Comportament, Departament de Ciències Experimentals i de la Salut, Universitat Pompeu Fabra, PRBB, C/ Dr. Aiguader 80, 08003, Barcelona, Spain.
Abstract
INTRODUCTION: 3, 4-Methylenedioxymethamphetamine (MDMA) and cannabis are widely abused illicit drugs that are frequently consumed in combination. Interactions between these two drugs have been reported in several pharmacological responses observed in animals, such as body temperature, anxiety, cognition, and reward. However, the interaction between MDMA and cannabis in addictive processes such as physical dependence has not been elucidated yet. DISCUSSION: In this study, the effects of acute and chronic MDMA were evaluated on the behavioral manifestations of Delta(9)-tetrahydrocannabinol (THC) abstinence in mice. THC withdrawal syndrome was precipitated by injecting the cannabinoid antagonist rimonabant (10 mg/kg, i.p.) in mice chronically treated with THC and receiving MDMA (2.5, 5 and 10 mg/kg i.p.) or saline just before the withdrawal induction or chronically after the THC administration. RESULTS: Both chronic and acute MDMA decreased in a dose-dependent manner the severity of THC withdrawal. In vivo microdialysis experiments showed that acute MDMA (5 mg/kg, i.p.) administration increased extracellular serotonin levels in the prefrontal cortex, but not dopamine levels in the nucleus accumbens. Our results also indicate that the attenuation of THC abstinence symptoms was not due to a direct interaction between rimonabant and MDMA nor to the result of the locomotor stimulating effects of MDMA. CONCLUSION: The modulation of the cannabinoid withdrawal syndrome by acute or chronic MDMA suggests a possible mechanism to explain the associated consumption of these two drugs in humans.
INTRODUCTION: 3, 4-Methylenedioxymethamphetamine (MDMA) and cannabis are widely abused illicit drugs that are frequently consumed in combination. Interactions between these two drugs have been reported in several pharmacological responses observed in animals, such as body temperature, anxiety, cognition, and reward. However, the interaction between MDMA and cannabis in addictive processes such as physical dependence has not been elucidated yet. DISCUSSION: In this study, the effects of acute and chronic MDMA were evaluated on the behavioral manifestations of Delta(9)-tetrahydrocannabinol (THC) abstinence in mice. THC withdrawal syndrome was precipitated by injecting the cannabinoid antagonist rimonabant (10 mg/kg, i.p.) in mice chronically treated with THC and receiving MDMA (2.5, 5 and 10 mg/kg i.p.) or saline just before the withdrawal induction or chronically after the THC administration. RESULTS: Both chronic and acute MDMA decreased in a dose-dependent manner the severity of THC withdrawal. In vivo microdialysis experiments showed that acute MDMA (5 mg/kg, i.p.) administration increased extracellular serotonin levels in the prefrontal cortex, but not dopamine levels in the nucleus accumbens. Our results also indicate that the attenuation of THC abstinence symptoms was not due to a direct interaction between rimonabant and MDMA nor to the result of the locomotor stimulating effects of MDMA. CONCLUSION: The modulation of the cannabinoid withdrawal syndrome by acute or chronic MDMA suggests a possible mechanism to explain the associated consumption of these two drugs in humans.
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: Heidi M B Lesscher; Emily Hoogveld; J Peter H Burbach; Jan M van Ree; Mirjam A F M Gerrits Journal: Eur Neuropsychopharmacol Date: 2005-01 Impact factor: 4.600
Authors: Patricia Robledo; Victoria Mendizabal; Jordi Ortuño; Rafael de la Torre; Brigitte L Kieffer; Rafael Maldonado Journal: Eur J Neurosci Date: 2004-08 Impact factor: 3.386