Altered gene expression of kappa opioid system, BDNF and nociceptin system on mesolimbic brain areas after prenatal alcohol exposure

WILLE-BILLE, ARANZA; PAUTASSI, RICARDO; D'ADDARIO, CLAUDIO

Puerto Varas

Congreso; VIII LASBRA INTERNATIONAL MEETING: ?Neurobiological basis of alcoholism: from molecules to behavior?; 2017

LASBRA

Altered gene expression of kappa opioid system, BDNF and nociceptin system on Mesolimbic Brain Areas after Prenatal Alcohol Exposure.Wille-Bille, A.1; Pautassi, R.M.1,2; D?Addario, C.31 Insituto de Investigaciones Médicas Mercedes y Martín Ferreyra, INIMEC-CONICET-UNC, Córdoba, Argentina.2 Facultad de Psicología, UNC, Córdoba, Argentina.3 Università degli Studi di Teramo, Teramo, Italia.aranza.wb@gmail.comModerate prenatal alcohol exposure (PEE, 1-2 g/kg, gestational days 17 to 20, GDs 17-20) heightens subsequent ethanol consumption in infant or adolescent rats. This effect may result from 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 gene expression of opioid systems, within mesocorticolimbic areas, after PEE.Pregnant Wistar rats received daily intragastric administration of alcohol (0.0 or 2.0 g/kg, GDs 17-20). The female and male offspring were analyzed, during infancy and adolescence, for gene expression levels of predynorphin (PDYN), nociceptin (NOC), kappa opioid or nociceptin (KOR and NOP, respectively) receptors and brain-derived neurotrophic factor (BDNF), in several areas of the mesocorticolimbic pathway.PEE induced enhanced gene expression levels of PDYN in Ventral Tegmental Area (VTA, during infancy only) and KOR in VTA and Prefrontal Cortex (PC), at both ages. Gene expression of NOC was significantly elevated in Nucleus Accumbens (NA). PEE heightened the levels of NOP in PC, but reduced its levels in VTA. Finally, the PEE animals exhibited lower levels of BDNF. These results suggest that a moderate level of alcohol exposure during pregnancy results in complex, region dependent, alterations in gene expression of opioid systems within the ,limbic system. Specifically, the pattern observed suggest an ethanol induced upregulation of the kappa system, which seems to be counteracted at the NA by an upregulation of the nociceptin system.