Gender differences in the effects of cannabidiol on ethanol binge drinking in mice
Autor: | María Salud García-Gutiérrez, Adrián Viudez-Martínez, Jorge Manzanares |
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Přispěvatelé: | Instituto de Salud Carlos III, Ministerio de Economía y Competitividad (España) |
Jazyk: | angličtina |
Rok vydání: | 2020 |
Předmět: |
Male
medicine.medical_specialty Cannabinoid receptor Alcohol Drinking Tyrosine 3-Monooxygenase medicine.medical_treatment Receptors Opioid mu Medicine (miscellaneous) Binge drinking Self Administration Nucleus accumbens Nucleus Accumbens Binge Drinking 03 medical and health sciences chemistry.chemical_compound Mice Random Allocation 0302 clinical medicine Sex Factors Receptor Cannabinoid CB1 Internal medicine medicine Animals Cannabidiol RNA Messenger Pharmacology Ethanol Tyrosine hydroxylase Behavior Animal business.industry Central Nervous System Depressants 030227 psychiatry Ventral tegmental area Psychiatry and Mental health medicine.anatomical_structure Endocrinology chemistry Female Cannabinoid business 030217 neurology & neurosurgery medicine.drug |
Zdroj: | Digital.CSIC. Repositorio Institucional del CSIC instname |
Popis: | The purpose of this study was to explore the effects of cannabidiol (CBD) on binge drinking and evaluate potential gender‐related differences. To this aim, male and female C57BL/6J mice (n = 60 per sex) were exposed to the drinking in the dark (DID) model for 4 weeks (DID‐1 to DID‐4). Dose‐response effects of CBD on the ethanol intake were tested by acute (day‐4 of DID‐3) or repeated administration (day‐1 to 4 of DID‐4) (experiment 1: CBD 15, 30, and 60 mg/kg, i.p.; experiment 2: CBD 90 mg/kg, i.p.). Finally, we analyzed the relative gene expression of tyrosine hydroxylase (TH ) and μ‐opioid receptor (OPRM1 ) and cannabinoid CB1 receptor (CB 1 r ) in the ventral tegmental area (VTA) and in the nucleus accumbens (NAc), respectively, by real‐time quantitative PCR. Females exhibited higher ethanol intake during each DID session. Interestingly, females also showed higher expression of TH and OPRM1 , without any difference in CB 1 r . Only the acute administration of CBD at the highest dose (90 mg/kg) reduced significantly ethanol consumption in both sexes. Chronic CBD administration (30, 60 and 90 mg/kg) reduced ethanol intake in males, whereas in females a significant reduction was only achieved with the highest dose (90 mg/kg). Repeated administration with CBD (60 mg/kg) significantly reduced TH and OPRM1 in males. In addition, CBD (30 and 60 mg/kg) significantly reduced CB1r in males. No effect was observed in females. Taken together, these findings suggest that CBD may be of interest for treating binge‐drinking patterns and that gender‐related difference may affect the treatment outcome. This research was supported by “Instituto de Salud Carlos III” (RETICS, RD12/0028/0019 and RD16/0017/0014), “Plan Nacional Sobre Drogas” (PNSD 2016/016), and “Ministerio de Economía y Competitividad” (FIS, PI14/00438) to JM. AVM is a predoctoral fellow supported by “Plan Nacional Sobre Drogas” (PNSD 2016/016). |
Databáze: | OpenAIRE |
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