As naltrexone has activity at multiple opioid receptor classes, it remains unknown where in the brain naltrexone exerts its clinical effects. All three opioid receptor classes (i.e., mu, kappa, delta) are present in the nucleus accumbens and other areas associated with the reinforcing effects of alcohol, like the ventral pallidum (VP) (Mansour et al., 1988), and pre-clinical research has demonstrated that the roles of specific receptor classes in these areas are complex. DAMGO, a selective mu opioid antagonist, microinjected in the VP suppresses voluntary alcohol consumption, while morphine had the opposite effect (Kemppainen et al., 2012). Microinjection of CTOP (mu antagonist) in the nucleus accumbens, however, failed to alter alcohol intake in animals (Hyytia and Kiianmaa, 2001). Likewise, delivery of delta or kappa agonists and antagonists, as well as naltrexone, in the VP had no effect on alcohol intake in rats (Kemppainen et al., 2012). These data stand in contrast to other studies examining delta and kappa effects on drinking. Delta opioid agonists specific to the delta opioid receptor sub-type one administered subcutaneously reduced drinking in mice, while a non-subtype-specific
