THE ENDOGENOUS OPIOID PEPTIDES IN REINFORCED BEHAVIORS (ENDORPHINS, STRESS, REWARD, AUTORADIOGRAPHY)

Recently, there has been active investigation into the role of the Endogenous Opioid Peptides (EOPs) in normal physiologic function and how alterations in activity of these peptides might contribute to different behavioral states. One putative function of the EOPs is to modulate reward quality information received by the brain as evidenced by their ability to act as reinforcers. In addition, the EOPs are also known to play a significant role in pain modulation. As such, the EOPs have been shown to be released from both pituitary and brain in response to several stressors. Since stress seems to produce an affective state opposite to that of reward, this dissertation investigated the involvement of the EOPs in the neural mechanisms of stress and reward. Initial behavioral studies looked at the effects of central injections of opiate receptor agonists and antagonists on water consumption in water deprived rats. Results indicated that opioid agonists and an antagonist reduced water intake in a dose and site specific manner. The injections were effective in areas previously implicated in both drinking and reward. These studies demonstrated the ability of the EOPs to alter a behavioral response to a natural reinforcer. Subsequently, radioimmunoassays of microdissected brain areas were used to assess changes in the levels of three different EOPs following acute and chronic running. Results indicated that the stress due to running was the only factor influencing central EOP levels with no effects observed for exercise training or running per se. A novel technique of in vivo autoradiography of opiate receptors was used to determine changes in opiate receptor occupancy in response to stress and reward. Changes in binding of a labeled opiate receptor antagonist in the presence of intracranial brain stimulation (ICS) and footshock (FS) was used to reflect EOP release due to these stimuli. Results indicated that ICS can inhibit EOP release in brain areas implicated in reward and may also possess an aversive component that causes EOP alterations similar to FS. Using this same technique opiate receptor occupancy changes occurring as a result of water deprivation and drinking were determined. This study indicated altered EOP release due to water deprivation stress. Subsequent presentation of water reversed this effect on receptor binding in putative brain reward areas. Thus, using several experimental approaches, new insights into the neuronal mechanisms and anatomical loci involved in opioid peptide modulation of reward information has been gained