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Sigma-1 antagonism inhibits binge ethanol drinking at adolescence

Agustín Salguero

  • Córdoba,
  • Argentina
  • Agustín Salguero ¹
  • , Leandro Ruiz-Leyva ²
  • , Ignacio Morón ³
  • , Enrique Portillo-Salido ⁴
  • , Cruz Miguel Cendán ²
  • , Rodrigo García Virgolini ¹
  • , Ricardo Marcos Pautassi ¹
  • 1 Instituto de Investigación Médica M. y M. Ferreyra (INIMEC–CONICET-Universidad Nacional de Córdoba), Córdoba, C.P. 5000, Argentina
  • 2 Department of Pharmacology, Faculty of Medicine, University of Granada, Spain
  • 3 Department of Psychobiology and Centre of Investigation of Mind, Brain, and Behaviour (CIMCYC), University of Granada, Spain
  • 4 Drug Discovery and Preclinical Development, Esteve Pharmaceuticals, Parc Científic de Barcelona, Barcelona, Spain

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. 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. 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.