Role of the kappa opioid system on the facilitating effects of Prenatal Alcohol Exposure on later alcohol intake

PAUTASSI R.M.; WILLE-BILLE, ARANZA; DADARIO C.

St Julian's

Congreso; Mediterranean Neuroscience Society Meeting 2017; 2017

Mediterranean Neuroscience Society Meeting 2017

Role of the kappa opioid system on the facilitating effects of Prenatal Alcohol Exposure on later alcohol intake.Several experiments indicated that moderate prenatal alcohol exposure (PEE, 1-2 g/kg, gestational days 17 to 20) induces a significant, facilitatory effect on subsequent ethanol consumption in infant or adolescent rats. This effect may be the consequence of PEE enhancing or reducing the appetitive and aversive motivational effects of ethanol, respectively. The mechanisms underlying PEE effects are, however, still elusive. The endogenous opioid system has been proposed as an important target of alcohol?s actions and ethanol exposure seems to alter the developmental trajectory of opioid systems, possibly affecting the hedonic effect of ethanol. The aim of this study was to describe the effect of PEE on subsequent, voluntary alcohol consumption, and on opioid system gene expression.Pregnant rats received daily intragastric administration of alcohol (0.0 or 2.0 g/kg). Female and male offspring were tested at infancy or adolescence. We analyzed anxiety response and ethanol-induced locomotor activity (infants and adolescents), alcohol intake (adolescents), and gene expression levels of predynorphin (PDYN) and kappa opioid receptors (KOR) in mesocorticolimbic areas of the brain (infants and adolescents).PEE was associated with elevated anxiety response in infants and with a blunted response to the stimulant effects of ethanol during adolescence. PEE male, adolescent, rats consumed signficantly higher amounts of alcohol than control peers. Notably, several PEE-induced alterations on gene expression were observed. During infancy, PEE signficantly enhanced levels of KOR in Prefrontal Cortex and PDYN in Ventral Tegmental Area (VTA), and signficantly lowered levels of PDYN in Nucleus Accumbens. PEE adolescents exhibited higher levels of KOR in VTA, than control rats.These results confirm that a moderate exposure to alcohol during the last days of pregnancy is a risk factor for subsequent ehancenment of alcohol intake at adolescence. The study also pinpoints alterations in behavior and gene expression that could underlie the facilitatory effects of PEE upon alcohol intake.