The CNS contains multiple opioid peptides and receptor types with heterogeneous regional distributions. The relationships between specific opioid peptides and receptor types in physiological circuits have not yet been determined. Similarly, while the opioid system has been implicated in numerous behavioral functions, the particular peptide-receptor type combinations that are involved remain to be determined. This laboratory is concerned with elucidating endogenous opioid mechanisms that regulate motivated behavior. To investigate the involvement of particular opioid peptides, highly specific antibodies are infused into discrete CNS regions and the effect of selective peptide inactivation on behavior is determined. To investigate the involvement of particular opioid receptor types, recently developed antagonists for mu, delta, and kappa receptors are infused into CNS regions and the effect of selective receptor blockade on behavior is determined. The long-term goal of this research is to identify the specific opioid peptide-receptor type combinations, within specific CNS regions, that regulate ingestive behavior, brain stimulation reward, and pain/aversion. To study ingestive behavior, lateral hypothalamic electrical stimulation is employed to elicit feeding. Previous results indicate that endogenous opioids sustain feeding behavior and probably do so by mediating the incentive properties of palatable taste. This research could improve our understanding of the mechanism through which the hedonic response to food determines intake. There is evidence that electrical brain stimulation reward (BSR) is homologous to natural consummatory reward. If so, the finding that food deprivation activates an opioid mechanism that potentiates BSR may offer a model for studying the way in which biological drive states control behavior by potentiating the reward value of stimuli that lead to drive reduction. Elucidation of this mechanism could provide insight not only into the physiological determinants of hedonic responses, but perhaps also unnatural compulsions such as drug abuse and addiction. Finally, electrical stimulation of the feeding/reward system in lateral hypothalamus also diminishes pain and aversion. This effect is opioid mediated and may be a collateral action of the food motivational system that protects food-seeking/consumption from disruption by certain types of noxious stimuli. If so, elucidation of this mechanism could provide insight into certain chronic pain and eating disorders where normal motivated behavior is disrupted by the intrusion of aversive sensations.
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