Antonia Serrano1,2, Evelyn Vadas3,4, Belen Ferrer3,4, Ainhoa Bilbao5, Noelia Granado6, Juan Suárez3,4, Francisco Javier Pavon3, Rosario Moratalla6, Fernando Rodríguez de Fonseca7,8. 1. Instituto IBIMA, Unidad de Gestión Clínica de Salud Mental, Hospital Regional Universitario de Málaga, 29010, Malaga, Spain. antonia.serrano@ibima.eu. 2. Laboratorio de Medicina Regenerativa, Instituto IBIMA, Hospital Regional Universitario de Málaga, Av. Carlos Haya 82, sótano., 29010, Malaga, Spain. antonia.serrano@ibima.eu. 3. Instituto IBIMA, Unidad de Gestión Clínica de Salud Mental, Hospital Regional Universitario de Málaga, 29010, Malaga, Spain. 4. Laboratorio de Medicina Regenerativa, Instituto IBIMA, Hospital Regional Universitario de Málaga, Av. Carlos Haya 82, sótano., 29010, Malaga, Spain. 5. Institute of Psychopharmacology, Central Institute of Mental Health, Medical Faculty of Mannheim, University of Heidelberg, Heidelberg, Germany. 6. Instituto Cajal, Consejo Superior de Investigaciones Cientificas (CSIC), 28002, Madrid, Spain. 7. Instituto IBIMA, Unidad de Gestión Clínica de Salud Mental, Hospital Regional Universitario de Málaga, 29010, Malaga, Spain. fernando.rodriguez@ibima.eu. 8. Laboratorio de Medicina Regenerativa, Instituto IBIMA, Hospital Regional Universitario de Málaga, Av. Carlos Haya 82, sótano., 29010, Malaga, Spain. fernando.rodriguez@ibima.eu.
Abstract
RATIONALE: The emergence of the consumption of highly potent synthetic cannabinoid receptor agonists (spice drugs) that produce important neurological symptoms has prompted the research on the consequences of acute and chronic use of these new psychoactive substances. Most studies on cannabinoid dependence have been performed in male animals, and there is a need of studies using female subjects. OBJECTIVES: In the present study, we evaluated only in female animals the role of dopamine D1 receptors in the behavioral responses induced by acute and repeated stimulation of cannabinoid CB1 receptors, including the development of physical dependence, since cannabinoid CB1 receptors are co-localized with dopamine D1 receptors on GABAergic neurons projecting to the substantia nigra. METHODS: To this end, female dopamine D1 receptor-deficient mice and wild-type littermates were treated with HU-210, a potent synthetic cannabinoid agonist. RESULTS: Mutant mice displayed an enhanced response to acute motor and hypothermic effects to HU-210 when compared with wild-type females. The administration of SR141716A precipitated behavioral signs of withdrawal in mice treated subchronically with HU-210. Severity of cannabinoid withdrawal syndrome was potentiated in dopamine D1-deficient female mice. Indeed, 4 of 6 abstinence signs were increased in mutant mice. CONCLUSIONS: These results support for a role of dopamine D1 receptors in the acute, chronic, and withdrawal actions of spice drugs.
RATIONALE: The emergence of the consumption of highly potent synthetic cannabinoid receptor agonists (spice drugs) that produce important neurological symptoms has prompted the research on the consequences of acute and chronic use of these new psychoactive substances. Most studies on cannabinoid dependence have been performed in male animals, and there is a need of studies using female subjects. OBJECTIVES: In the present study, we evaluated only in female animals the role of dopamine D1 receptors in the behavioral responses induced by acute and repeated stimulation of cannabinoid CB1 receptors, including the development of physical dependence, since cannabinoid CB1 receptors are co-localized with dopamine D1 receptors on GABAergic neurons projecting to the substantia nigra. METHODS: To this end, female dopamine D1 receptor-deficient mice and wild-type littermates were treated with HU-210, a potent synthetic cannabinoid agonist. RESULTS: Mutant mice displayed an enhanced response to acute motor and hypothermic effects to HU-210 when compared with wild-type females. The administration of SR141716A precipitated behavioral signs of withdrawal in mice treated subchronically with HU-210. Severity of cannabinoid withdrawal syndrome was potentiated in dopamine D1-deficient female mice. Indeed, 4 of 6 abstinence signs were increased in mutant mice. CONCLUSIONS: These results support for a role of dopamine D1 receptors in the acute, chronic, and withdrawal actions of spice drugs.
Authors: F Rodríguez de Fonseca; P Rubio; F Menzaghi; E Merlo-Pich; J Rivier; G F Koob; M Navarro Journal: J Pharmacol Exp Ther Date: 1996-01 Impact factor: 4.030