Prenatal ethanol exposure affects intake and motivational properties of ethanol during infancy: possible mechanisms of action

NIZHNIKOV ME; PAUTASSI RM; VARLINSKAYA L; SPEAR, N.E.

Sapporo

Congreso; 2012 International Society for Biomedical Research on Alcoholism (ISBRA) World Congress; 2012

Science Council of Japan

Prenatal exposure to ethanol in humans is a common and widespread phenomenon. Prenatal exposure to high doses of ethanol often leads to fetal alcohol syndrome (FAS) (i.e. Ornoy and Ergaz, 2010; Riley and McGee; 2005), whereas low to moderate prenatal exposure may not result in full-blown FAS but may lead to enhanced drinking during adolescence and later in life (Alati et al., 2006, 2008). Prior to these epidemiological studies, prenatal ethanol exposure in the laboratory rodent was shown to increase subsequent ethanol intake during both infancy and adolescence (e.g., Arias and Chotro, 2005; for review of earlier studies, see Spear & Molina, 2005). The neural mechanisms responsible for this effect of prenatal ethanol have yet to be fully investigated. It is widely recognized that the reinforcing properties of ethanol largely depend on its pharmacological effects and that opioid systems are closely linked to these effects (Lewis, 1990; Herz, 1997). Among the many neurochemical systems involved in ethanol intake and reinforcement, the endogenous dynorphin/kappa opioid receptor system is of great interest, given its involvement in regulation of ethanol intake via positive or aversive properties (Herz, 1997; Shippenberg et al., 2007). Of critical importance is that changes in opioid expression due to prenatal and postnatal ethanol exposure have been seen in infant and adult animals (Walker and Koob, 2008; Walker et al., 2011). The current presentation will review some of the work performed in our laboratory demonstrating changes in responding to ethanol following brief prenatal experience with low doses of alcohol. Both intake of ethanol and appetitive ethanol reinforcement are increased by prenatal exposure to moderate doses of ethanol. This phenomenon will be discussed in terms of a variety of models and dependant measures. Furthermore, age-related changes in mechanisms involved in the increased intake and conditioning to ethanol will be discussed. Finally a tentative hypothesis relevant to the ontogenetic changes in kappa opioid function leading to a greater predisposition for ethanol intake and appetitive reinforcement following prenatal ethanol exposure will be discussed.