Brief prenatal ethanol exposure alters the expression of dynorphin- and nociception-related genes in the infant and adolescent brain

PAUTASSI R.M.

San Diego

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

Research Society on Alcoholism (RSA)

We have found that prenatal ethanol exposure (PEE, 2.0 g/kg; gestational days 17?20) increasesthe rewarding effects of ethanol, and heightens ethanol-induced activation of themesocorticolimbicpathway and ethanol intake in adolescence. These effects may be the result of a PEE-induced dysregulationof the kappa opioid receptor (KOR) system. We investigated, in infant and adolescent ratsexposed to PEE, brain expression of dynorphin (DYN) and nociceptin (NOC) related genes andassessed anxiety-like behavior. PEE rats exhibited greater avoidance of the brightly lit areas in thelight-dark box (LDB) and in the concentric square field (CSF) test, greater preference for the shelteredarea in the CSF test and hypoactivity in the open field (OF). These effects were associated withupregulated PDYN and KOR mRNA levels in the ventral tegmental area (VTA) and KOR mRNAlevels in the prefrontal cortex. The changes in the VTA were accompanied by a reduction of DNAmethylation at the PDYN gene promoter, and by lower NOC receptor gene expression. PEE ratsalso had lower PDYN ? yet greater NOC? gene expression in the nucleus accumbens. These resultssuggest that PEE upregulates the dynorphin system, resulting in an anxiety-prone phenotype, andtriggering compensatory responses in the nociceptin system.