The aims of this proposal are to characterize the neuronal mechanisms underlying age-dependent plasticity of mesotelencephalic dopamine (DA) systems in rats. The literature suggests that the neural and behavioral effects of mesotelencephalic DA depletions are highly dependent upon the animal's age at the time of damage. Animals depleted during development are spared from the severe deficits in self-stimulation and sensorimotor function seen in comparably depleted adults. Moreover, the specific neural mechanisms underlying this sparing phenomenon differ as a function of age at the time of damage. These various forms of plasticity involve age-related changes in the functional interactions between D1 and D2 DA receptor subtypes. This proposal will allow our laboratory to establish two new techniques in order to further reveal the mechanisms underlying this age-dependent plasticity. First, we will employ IN VIVO MICRODIALYSIS IN FREELY MOVING ANIMALS in order to determine whether the age-related changes in the contributions of Dl and D2 receptors to behavior are paralleled by similar changes in the D1 and D2 mediation of DA, ACh, and GABA release within the basal ganglia. Such studies may reveal critical synapses associated with the sparing from deficits in sensorimotor and self-stimulation behavior. Second, we will utilize QUANTITATIVE DA RECEPTOR AUTORADIOGRAPHY to determine whether there are age-related changes in the density and/or distribution of D1 and D2 receptors that parallel the age-dependent effects of D1 and D2 receptors on behavior. Mesotelencephalic DA systems are involved in a wide range of behaviors, including; reward functions, self-stimulation, attention, and sensorimotor integration. Dysfunctions within these DA systems are associated with a variety of disorders relevant to mental health, including; drug abuse, learning deficits, affective disorders, Parkinson's disease, and schizophrenia. The results obtained from this proposal will provide insights into the neurochemical and neuroanatomical bases for plasticity in sensorimotor and self-stimulation behavior and how age constrains the extent of this plasticity.
