RT Journal Article
T1 Cessation of fluoxetine treatment increases alcohol seeking during relapse and dysregulates endocannabinoid and glutamatergic signaling in the central amygdala.
A1 Suarez, Juan
A1 Khom, Sophia
A1 Alen, Francisco
A1 Natividad, Luis A
A1 Varodayan, Florence P
A1 Patel, Reesha R
A1 Kirson, Dean
A1 Arco, Rocio
A1 Ballesta, Antonio
A1 Bajo, Michal
A1 Rubio, Leticia
A1 Martin-Fardon, Remi
A1 Rodriguez de Fonseca, Fernando
A1 Roberto, Marisa
K1 Alcohol
K1 Amygdala
K1 Antidepressant
K1 Cannabinoid
K1 Glutamate
K1 Relapse
AB 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.
PB Wiley
YR 2019
FD 2019-06-27
LK http://hdl.handle.net/10668/14298
UL http://hdl.handle.net/10668/14298
LA en
NO Suárez J, Khom S, Alén F, Natividad LA, Varodayan FP, Patel RR, et al. Cessation of fluoxetine treatment increases alcohol seeking during relapse and dysregulates endocannabinoid and glutamatergic signaling in the central amygdala. Addict Biol. 2020 Sep;25(5):e12813
DS RISalud
RD Apr 7, 2025