The goal of this project is to locate at least part of the neural substrate supporting the rewarding nature of brain stimulation in the rat. Initial experiments will examine the effects on medial forebrain bundle self-stimulation of lesions that destroy specific regions of the mid- and hindbrain. Follow-up experiments will employ cell-body-specific neurotoxins to determine whether the lesions are disrupting reward-relevant cell bodies, or axons en passant or terminals. Electrophysiological techniques will then be used to determine whether the areas where lesions are effective have direct axonal connections to medial forebrain bundle self- stimulation sites. If the two sites are directly connected, then compound action potentials generated at one site can be recorded with a consistent latency, amplitude, and duration at the other site. If a direct axonal connection exists, compound action potential recording will demonstrate whether the conduction properties of the axons linking the two sites are compatible with psychophysically-based estimates of the conduction properties of medial forebrain bundle axons that carry the reward signal. It is important to locate these reward-relevant sites because future electrophysiological experimentation will be aimed at (1) determining whether areas where lesions are effective may contain cells directly activated by rewarding brain stimulation; (2) determining whether these cells have the conduction properties characteristic of the substrate for self-stimulation; and (3) discovering which properties of survival-relevant stimuli such as food, water, and,shelter alter these cells' activity. The long range goal of this work is to understand how the substrate for brain stimulation reward acts to control motivated, goal- oriented behavior in the natural environment. It has been amply demonstrated that this substrate has neurochemical (if not anatomical) links to midbrain dopaminergic systems important in addictive behaviors, particularly drug abuse. Furthermore, activation of the substrate can elicit avid consumption of and interaction with motivationally-relevant goal objects such as food or receptive mating partners in the absence of physiological need. Thus, understanding the operation of this neural system should shed light on the operation of systems that underlie both normal motivational functioning, and the abnormal human behaviors of addiction, drug abuse, and compulsive consumption.
