Selection for high and low ethanol intake during adolescence yields differential ethanol-induced locomotion, anxiety response and fos immunoreactivity

FERNANDEZ M.; DE OLMOS, S; FERREYRA, A.; CHINER, F.; BORDON, A; ESPINOSA, L.; PAUTASSI R.M.

San Diego

Congreso; 2018 Meeting of the Research Society on Alcoholism (RSA); 2018

Research Society on Alcoholism (RSA)

There are several lines of rats selectively bred for low or high ethanol intake during adulthood (e.g.,alcohol preferring and non-preferring rats). These are valuable models for assessing determinants ofethanol use and dependence. To our knowledge, however, none of these lines have been selectedfor ethanol intake during adolescence, a developmental stage in which ethanol use normativelybegins and, often, escalates. We performed, in genetically heterogeneousWistar rats and acrossthree filial generations, a short-term selective breeding program, as a function of low- or high-ethanolintake during adolescence. The program yielded, as expected, significant differences in ethanolintake and preference between the lines.We also observed several other behavioral and neural differencesbetween the lines. In the present study wemeasured, in adolescent Wistar rats derivedfrom parents that were selected for high (STDRHI line) or low (STDRLO line) ethanol consumption,anxiety reactivity (Exp. 1), baseline and ethanol-inducedmotor activity (Experiment 2) and baselineand ethanol-induced neural activity (Experiment 3). STDRHI rats exhibited, when compared toSTDRLO peers: (a) significantly less time spent in the white area of a light-dark box test and heightenedtaste neophobia, (b) heightened ethanol-induced (1.25 and 2.5 g/kg)motor activity in an openfield, with some sex differences and (c) a complex pattern of baseline (0.0 g/kg) and ethanol-induced(1.25 or 2.5 g/kg ethanol) Fos immunoreactivity (ir). Specifically, baseline Fos-ir was significantlygreater in STDRHI than in STDRLO rats, across all areas measured (central, basolateral and medialamygdaloid nucleus [Bla, Cem andMe, respectively]; nucleus accumbens core [AcbC] and shell[AchSh], ventral tegmental area [VTA] and pre- and infralimbic prefrontal cortex [PrL and IL]).STDRHI, but not STDRLO, rats exhibited ethanol-induced Fos-ir in Me, yet the inverse pattern wasfound in Cem, and there was an ethanol-induced Fos-ir depression in the AcbC of STDRHI rats only.These results suggest that selection for high ethanol drinking during adolescence is associated withheightened sensitivity to the stimulating effects of the drug, an anxiety-prone phenotype that correlateswith basal neural hyperexcitability in amygdala and in themesocorticolimbic pathway, as wellas with an altered pattern of neural response to ethanol?s pharmacological effects.