Sigma-1 antagonism inhibits binge ethanol drinking at adolescence Cendán Martínez, Cruz Miguel Ruiz Leyva, Leandro Morón Henche, Ignacio Ethanol sigma-1 receptors Rats Adolescence Binge Drinking Sex differences Background: Ethanol use during adolescence is a significant health problem, yet the pharmacological treatments to reduce adolescent binge drinking are scarce. The present study assessed, in male and female adolescent Wistar rats, if the sigma-1 receptor (S1-R) antagonists S1RA or BD-1063 disrupted ethanol drinking. Methods: Three times a week, for two weeks, the rats received the S1-R antagonists. Thirty min later they were exposed, for 2 h, to a bottle of 8% or 10 % v/v ethanol. A 24 h, two-bottle, ethanol intake test was conducted after termination of these procedures. A subset of these rats was tested for recognition memory via the novel object recognition test. Results: The rats given 64 mg/kg S1RA drank, in each binge session, significantly less than vehicle counterparts. Male rats given 4 or 16 mg/kg S1RA drank significantly less than those given 0 mg/kg in session 3 or in session 1 and 2, respectively; whereas female rats given 4 or 16 mg/kg drank significantly less than females given 0 mg/kg in session 2-5 or in sessions 2-6, respectively. Administration of 32 mg/kg, but not of 2 or 8 mg/kg, BD-1063 suppressed, across sessions, ethanol drinking. S1-R antagonism reduced absolute ethanol drinking at the two-bottle choice post-test. Recognition memory was not affected by the ethanol exposure. Conclusions: The results indicate that S1-R antagonists may be promising targets to prevent increases in ethanol intake at adolescence. The persistent effect of S1-R antagonism in free-choice drinking suggests that modulation of the S1-R is altering plastic effects associated with ethanol exposure. 2024-02-01T08:49:51Z 2024-02-01T08:49:51Z 2020-08-06 journal article Ruiz-Leyva L, Salguero A, Morón I, Portillo-Salido E, Cendán CM, Pautassi RM. Sigma-1 antagonism inhibits binge ethanol drinking at adolescence. Drug Alcohol Depend. 2020;215:108214. doi:10.1016/j.drugalcdep.2020.108214 https://hdl.handle.net/10481/87876 10.1016/j.drugalcdep.2020.108214 eng http://creativecommons.org/licenses/by-nc-nd/4.0/ open access Attribution-NonCommercial-NoDerivatives 4.0 Internacional Elsevier