The proposed study on central monoaminergic neurons is designed to provide useful information on the functional development and growth of noradrenergic, dopaminergic and serotonergic neurons. Fluorescence microscopy will be used to visualize neuronal growth throughout the central nervous system (CNS). Functional development will be assessed by measuring active uptake and turnover processes in discrete regions of the CNS (neocortex, hippocampus, amygdala, striatum, septum, hypothalamus, thalamus, midbrain, pons-medulla, cerebellum and spinal cord), and such studies will serve to extend the histochemical data. A host of pharmacological agents will be administered to rats during the developmental stages to indicate possible critical subcellular sites associated with or necessary for ontogenetic development. Such studies will also indicate critical time periods in development, since it has already been shown that neuronal effects of various chemical agents are quite different in mature and neonatal animals. By using similar types of agents the importance of the blood-brain barrier in modulating effects will be assessed. Study of cholinergic neuronal development after pharmacological intervention may indicate critical types of neuron to neuron communication during development, whereby growth of one system influences growth of the other. Studies on neonatal lesioning of monoaminergic neurons will be followed to maturity in order to accurately quantitate any regenerative or sprouting phenomena. The proposed series of experiments will describe monoaminergic ontogeny and such related events as susceptibility to pharmacological substances during the process of development of the blood-brain barrier for these specific neuronal systems, inter-neuronal influences on development and regenerative/sprouting phenomena. BIBLIOGRAPHIC REFERENCES: McLean, J.H., R.M. Kostrzewa and J.G. May. Behavioral and biochemical effects of neonatal treatment of rats with 6-hydroxydopa. Pharmacol. Biochem. Behav. 4 (1976) 601-607. Kostrzewa, R.M. and R.E. Garey. Effects of 6-hydroxydopa on noradrenergic neurons in developing rat brain. J. Pharmacol. Exp. Ther. 197 (1976) 105-118.
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