Hill, and Coy ( 1979) reported enhanced reversal learning after the administration of an enkephalin analogue in the rhesus monkey. These basically consistent results with opiate agonists are not complimented by converse findings with the opiate antagonist naloxone. In fact, naloxone has been found to facilitate memory consolidation processes in both mice ( Izquierdo, 1979) and rats ( Messing, Jensen, Martinez, Speihler, Vasquez, Soumireu-Mourat, Liang, & McGaugh, 1979) and facilitated extinction of responding in a classical conditioning paradigm in rabbits ( Hernandez & Powell, 1980). In man, naloxone has produced a slowing of the averaged EEG ( Volavka, 1979); blocked ethanol-induced impairment on psychomotor tasks ( Jeffcoate et al., 1979); produced subtle ameliorating effects on manic symptoms; facilitated performance on simple behavioral attention tasks ( Gritz, Shiffman, Jarrik, Schlesinger, & Charavastra, 1976); and evoked altered potential correlates of attention in normal subjects ( Arnsten et al., 1981). Thus, although the endogenous opiates clearly have a role(s) in aspects of attention and memory processes, the precise nature of these effects, in a cognitive sense, will only be elucidated by future research. These apparent discrepancies are undoubtedly related to the ambiguities created by exogenous administration of opiate alkaloids and endogenous ligands, (which may differ markedly from physiological ligand-receptor interactions), and our present ignorance of the regulatory and feedback processes involved in normal enkephalinergic cellular activity. However, it may be hypothesized that significant reward-related effects on memory processes may actually be mediated at limbic structures that receive direct or indirect brainstem dopaminergic innervation, and have already been implicated in memory mechanisms. Structures such as the amygdala and hippocampus are prime candidates for consideration.
Recently, Gallagher, Kapp, Pascoe, and Applegate ( 1981) have presented evidence for opioid-æ receptor involvement in the time-dependent memory consolidation mechanisms mediated by the amygdala in rodents. Similarly, Routtenberg and colleagues ( Collier, Miller, Quirk, Travis, & Routtenberg, 1981) have reported data indicative of a role for endogenous opioids in both reward and memory functions of the hippocampus. They have postulated an endogenous- opiate substrate for a reinforcement system involved in working memory. Thus, studies of the neuropharmacology of "reward" pathways may hold the promise of heralding an understanding, at the cellular level, of the memory mechanisms mediated in these limbic structures, at which decades of classical neuropsychological analysis have hinted.
Altshuler H. I., Phillips P. E., & Feinhandler P. A. "Alteration of ethanol self-administration by naltrexone". Life Sciences, 1980, 26, 679-688.