D-058
Ethanol-induced taste aversion strength predicts subsequent ethanol-induced locomotion in adolescent male Wistar rats: modulation by sigma-1 receptor antagonism
Agustín Salguero1,4, Ignacio Morón3, Cruz Miguel Cendán2, Ricardo Marcos Pautassi1,4
  1. Instituto de Investigación Médica M. y M. Ferreyra (INIMEC – CONICET-Universidad Nacional de Córdoba)
  2. Department of Pharmacology, Institute of Neuroscience, Biomedical Research Center (CIBM) Faculty of Medicine, University of Granada, Spain
  3. Department of Psychobiology and Centre of Investigation of Mind, Brain, and Behavior (CIMCYC), Faculty of Psychology, University of Granada, Spain
  4. Facultad de Psicología, Universidad Nacional de Córdoba, Córdoba, Argentina
Presenting Author:
Agustín Salguero
asalguero@immf.uncor.edu
The balance between ethanol's appetitive and aversive effects affects vulnerability for alcohol use disorder (AUD). This balance can be modulated by drugs such as S1RA (a sigma-1 receptor antagonist that inhibits ethanol intake) and changes across the lifespan. More work is needed during the critical period of adolescence. We examined this relationship in adolescent Wistar rats using aversive trace conditioning and ethanol-induced locomotion. Rats were pretreated with S1RA (0 or 16mg/kg). Saccharin intake was followed by ethanol administration (30 min after saccharin, 2.5g/kg). Vehicle-treated rats did not develop aversion, but S1RA enabled robust taste aversion at PD32-36. At PD39, ethanol-induced locomotion was evaluated. Correlation analysis revealed, in ethanol-treated rats, a significant association between saccharin intake and ethanol-induced locomotion (r=0.62, p=0.01). Higher saccharin consumption (weaker aversion) predicted stronger locomotor activation. This association was absent in vehicle controls, reflecting ethanol-specific effects. The correlation emerged regardless of S1RA treatment, which also reduced locomotor stimulation. The results suggest that ethanol aversion predicts sensitivity to ethanol's stimulant effects. Aversive conditioning seems to be a marker for addiction vulnerability at adolescence. S1R antagonism shifts this balance to enhanced aversion and reduced stimulation, showing promise as a treatment for AUD.