IBN-9808865 LAY ABSTRACT The idea of a "reward system" in the brain has become popular in neuroscience in the past decade. The most common idea is of a single reward system; the favorite candidate for such a system is the mesoaccurnbens dopamine system, originating in the ventral tegmental area of the midbrain and terminating in the nucleus accumbens of the forebrain. The experiments in the proposal are designed to test the idea of two separate reward systems. One centered in the nucleus accumbens, receives a glutamatergic input from the subiculum and a dopaminergic input from the ventral tegmental area. It is involved in activating the motor programs of "appetitive" behaviors, such as exploration and locomotion. The second, centered in the ventrolateral striatum, receives a glutamatergic input from the sulcal prefrontal cortex and and dopaminergic input from the substantia nigra. It is involved in activating the motor programs of "consummatory" behaviors, particularly feeding. The experiments are largely devoted to behaviorally examining hypothesized roles of glutamatergic, dopaminergic, and GABAergic neurotransmission at the accumbens and ventrolateral striatal nodes of these functionally distinct systems. This will be done by intracerebral microinjections of drugs, which affect specific receptor subtypes of the glutamatergic, dopaminergic, and GABAergic systems. The injections are proposed to modify responding of rats for electrical self-stimulation of ventral subiculum or sulcal prefrontal cortex in ways consistent with known electrophysiological effects of these drugs. These experiments also emphasize the idea that these "reward systems" are actually "behavior systems," wherein dopamine modulates activity in hierarchically organized neural systems of cortical origin. Self-stimulation of subiculum and sulcal prefrontal cortex develops very slowly; the development seems dependent upon the number of stimulations, not the number of responses. Thus it appears more like neural activity- dependent plasticity than response-dependent learning. To examine this phenomenon, the investigators will test the idea that the development of this brain stimulation reward depends on activity at glutamate receptors of the NMDA subtype.