The primary objectives are to analyze the dynamic aspects of dopaminergic and cholinergic neurotransmitter activity (synthesis and release), the effects of drugs on this activity during development, and the interaction between the dopaminergic and cholinergic systems in the neostriatum of the developing rat pup.
The specific aims are: 1) to characterize the developmental neurochemistry of the striatal dopamine system in the rat, with respect to neurotransmitter synthesis and release, and to determine at what point in the course of development the dopaminergic system is functionally active; 2) to determine the mechanism by which amphetamine alters the release of dopamine in the developing rat pup; and 3) to examine the effect of the dopaminergic system on acetylcholine synthesis and release in the neostriatum of the developing rat pup. Drugs which are used clinically in the treatment of hyperkinetic children or Attention Deficit Disorder in children, such as amphetamine, decrease the release of striatal dopamine at early stages of development in the rat, when compared with the adult response. Using pharmacological manipulations and in vivo electrochemical techniques, we will determine the mechanism by which this paradoxical alteration in release, by amphtamine, occurs at this time in development. It has been shown that the dopaminergic and cholinergic systems interact in the neostriatum. However, it is not known whether these systems interact during development and, if so, the degree of this interaction. In the experiments proposed here, we will determine the influence of dopamine release on the cholinergic system in the neostriatum of the developing rat pup. These studies will provide information as to the development of synthesis and release in the dopaminergic and cholinergic system, the effects of drugs on this activity during development, and the degree of interaction between the dopaminergic and cholinergic systems in the neostriatum during development.
