Although exact neural mechanisms of this adolescent-associated insensitivity to aversive drug consequences are still unknown, there is some evidence that dynorphyn/kappa opioid receptor systems located within reward-related neurocircuitry may be involved in sensitivity to negative consequences of drugs, including cocaine and ethanol (Chefer et al., 2005; Zapata & Shippenberg, 2006). Increases in the activity of this endogenous opioid system oppose cocaine- or ethanol-induced activation of the mesolimbic DA system, thereby either decreasing positive rewarding effects of these drugs or even producing dysphoria (see Shippenberg et al., 2007). Our recent studies have shown that adolescent rats are relatively insensitive to social anxiogenic effects not only of ethanol (Varlinskaya & Spear, 2002), but also of the selective kappa agonist, U60,622E, with both drugs decreasing social investigation and transforming social preference into social avoidance (Varlinskaya & Spear, 2009). Work is ongoing to explore further the impact of ontogenetic differences in the kappa opioid system to adolescent insensitivities to adverse consequences of alcohol.
