Cessation of fluoxetine treatment increases alcohol seeking during relapse and dysregulates endocannabinoid and glutamatergic signaling in the central amygdala
Year: 2019
Type: article
Abstract: Administration of selective serotonin reuptake inhibitors (SSRIs), typically used as antidepressants, induces long-lasting behavioral changes associated with alcohol use disorder (AUD). However, the contribution of SSRI (fluoxetine)-induced alterations in neurobiological processes underlying alcohol relapse such as endocannabinoid and glutamate signaling in the central amygdala (CeA) remains largely unknown. We utilized an integrative approach to study the effects of repeated fluoxetine administration during abstinence on ethanol drinking. Gene expression and biochemical and electrophysiological studies explored the hypothesis that dysregulation in glutamatergic and endocannabinoid mechanisms in the CeA underlie the susceptibility to alcohol relapse. Cessation of daily treatment with fluoxetine (10 mg/kg) during abstinence resulted in a marked increase in ethanol seeking during re-exposure periods. The increase in ethanol self-administration was associated with (a) reductions in levels of the endocannabinoids N-arachidonoylethanolomine and 2-arachidonoylglycerol in the CeA, (b) increased amygdalar gene expression of cannabinoid type-1 receptor (CB1), N-acyl phosphatidylethanolamine phospholipase D (Nape-pld), fatty acid amid hydrolase (Faah), (c) decreased amygdalar gene expression of ionotropic AMPA (GluA2 and GluA4) and metabotropic (mGlu3) glutamate receptors, and (d) increased glutamatergic receptor function. Overall, our data suggest that the administration of the antidepressant fluoxetine during abstinence dysregulates endocannabinoid signaling and glutamatergic receptor function in the amygdala, facts that likely facilitate alcohol drinking behavior during relapse.
Source: Addiction Biology
DOI: 10.1111/adb.12813
Language: English
Subfield: Cellular and Molecular Neuroscience
Field: Neuroscience
Domain: Life Sciences
Open Access status: green
Funders: U.S. Department of State, European Commission, Austrian Science Fund, Ministerio de Educación, Cultura y Deporte, Ministerio de Economía y Competitividad, Ministerio de Sanidad, Servicios Sociales e Igualdad, National Institutes of Health, Plan Nacional sobre Drogas, Instituto de Salud Carlos III, European Regional Development Fund, National Institute on Alcohol Abuse and Alcoholism
Awards: G1075404386, G1147851069, Substance P effects on IlC-CeA circuit in alcoholism, Identification of novel mechanisms in alcohol-induced cognitive dysfunction, G1902745206, Neuroplasticity of the Extended Amygdala CRF circuitry in alcohol dependence, G213944693, G236340927, G2514289894, G2593618960, G2615643966, G270285381, G2708544407, Cross sensitization of diet and alcohol on binge behaviors and metabolic dysfunction, G3173115544, G3351098102, G3497339853, Hypothalamic oxytocin influence on extended amygdala CRF neurons in alcohol dependence, G4510042965, G4616156949, Lípidos transmisores derivados del ácido oleico: Estudio traslacional de su papel en los trastornos por uso de alcohol, G4854471686, G5013652837, G51370085, G5270255988, G56130422, G5895793718, G6487289758, G6491234253, G6605351877, G7281076513, G7421759427, Alcohol-induced neuroadapation of prefrontal cortical projections, G7636921007, G815887170, Gene-environment interaction: the brain CRF system in alcohol preferring msP rats, G8808751706, G8873198235, Obesidad infantil grave de comienzo precoz al diagnóstico y tras pérdida ponderal: Fundamentos metabólicos, hormonales, genéticos, genómicos, metabolómicos y de microbiota, G9000001140, G9000083576, G9000094387, G9000107746, G9000232254, G9000238883, G9000264711, G9000267263, G9000330413, G9000333065
OpenAlex ID: W2963934415