Intrastriatal cholinergic modulation of learning

University Of Wisconsin Madison, Madison WI

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Abstract

DESCRIPTION (provided by applicant): Early research into the pharmacological therapy of Parkinson's disease revealed important interactions of striatal dopamine and acetylcholine in normal basal ganglia function. This proposal will address muscarinic acetylcholine mechanisms involved in learning and performance of an operant task, and will examine if learning or motivational deficits caused by muscarinic blockade result from alterations of dopaminergic function. To assess striatal dependence on cholinergic activation for learning, muscarinic receptor blockade within subregions of nucleus accumbens and caudate of the rat will be applied during the acquisition of a bar-pressing response for sucrose reward. Additional experiments will assess whether cholinergic manipulations impact locomotor or feeding behavior in general, or if muscarinic antagonism may reduce the reinforcing value of sucrose. To test whether these manipulations affect behavior by inhibitory modulation of dopamine, rats will be pretreated with instrastriatal GBR 12909 (a dopaminergic agonist) prior to infusion of the cholinergic antagonist, in an attempt to reinstate normal barpressing behavior. Finally, to ascertain the interactions of acetylcholine and dopamine on neuronal activity as a whole, striatal c-fos immunohistochemistry will be assessed in response to intrastriatal manipulations of both acetylcholine and dopaminergic activation. These experiments should increase the understanding of the role of striatal muscarinic acetylcholine processes underlying learning, and its interactions with dopamine.