INIMEC - CONICET   05467
INSTITUTO DE INVESTIGACION MEDICA MERCEDES Y MARTIN FERREYRA
Unidad Ejecutora - UE
congresos y reuniones científicas
Título:
Ontogenetic differences in kappa opioid mediation of ethanol’s motivation properties
Autor/es:
NIZHNIKOV ME; PAUTASSI RM; VARLINSKAYA L; RAHMANI P; SPEAR, N.E.
Lugar:
Seattle
Reunión:
Congreso; Kappa Therapeutics: First Conference on the Therapeutic Potential of Kappa Opioids in Pain and Addiction; 2011
Resumen:
Ontogenetic differences in kappa opioid mediation of ethanol’s motivation properties.  Adult rodents exhibit aversions to conditioned stimulus (CS) paired with moderate to high doses of ethanol.  Conversely, rats one-week old or younger or tend to exhibit appetitive conditioned responses to these same CSs (Cheslock et al., 2000; Petrov et al., 2003; Nizhnikov et al., 2006a). This ethanol-mediated appetitive conditioning seems to fade during the second postnatal week. Akin to the results found with ethanol, our recent work has shown that neonate rats find kappa opioid stimulation appetitive (Petrov et al., 2006) while in adults kappa agonists induce robust aversions (Mucha & Herz, 1985; Hippenberg &Herz, 1986). Altogether these results suggest that the dynorphin/kappa opioid receptor system switches during early development from mediating appetitive to aversive reinforcement. It has been clearly demonstrated that the opioid system is involved in the reinforcing properties of EtOH (Vengeliene et al., 2008; Sommer et al., 2006; Méndez et al., 2008), with mu-delta and kappa receptors apparently mediating the appetitive and aversive motivational properties of ethanol in adults respectively (Mitchell et al., 2005; Logrip et al., 2009; Sandi et al., 1988; Matsuzawa et al., 1999). Data also suggest that EtOH exposure has a profound effect on the kappa opioid system and its mediation of EtOH intake changing receptor denseties and even the function of the kappa opioid system (Rosin et al., 1999; Lindholm et al., 2007; Walker and Koob 2008). The present set of experiments tested the reinforcing properties of ethanol and kappa opioid agonists across infancy using a classical taste conditioning model on one or two-week old pups(PD 4 vs PD12). Furthermore we examined the effects of kappa opioid antagonists on ethanol reinforcement across the same ages. The overarching hypothesis is that at least part of the differential effects of ethanol across age might be mediated by the kappa opioid system. The results indicate that 4 day-old rat pups find stimulation by ethanol and kappa opioid agonists positively reinforcing. Conversely, older infants (PD12) find kappa opioid agonists aversive. Furthermore, kappa opioid antagonists have opposite effects on ethanol’s reinforcing properties across age. Older subjects pretreated with nor-BNI (kappa opioid antagonist) prior to ethanol reinforcement exhibit appetitive responding to a flavor paired with ethanol compared to their saline controls. On the other hand, younger subjects no longer found ethanol positively reinforcing.