Dopaminergic Effects on the Integration of Motor-and Affective-Related Inputs to the Nucleus Accumbems

Grant Type
Grant Year
Institution Location
Institution Organization Name
University of Pittsburgh
Investigators Name
O’Donnell, Patricio, MD, PhD

A characteristic of Tourette Syndrome (TS) is that symptoms frequently appear under emotional pressure or in stressful circum¬stances. Therefore, there appears to be some measure of dysfunction in the interactions between neural systems involved in emotional and motor responses. A potential site for such interactions is the nucleus accumbens which is the limbic aspect of the striatal complex. The accumbens is connected with both motor-related and emotion-related neural circuits, receiving convergent inputs from the amygdala, hippocampus, and prefrontal cortex. Recently we have shown that neurons in this nucleus can be activated by their cortical inputs only when they are gated by activation of inputs originating in the hippocampus, which may control the flow of information within the nucleus accumbens in a context-sensitive manner. The aims of this project are to assess the role of dopamine on these interactions. Dopamine antagonists have been successful in treating TS symptoms, and a potential site for this effect may be their ability to modulate the integration of motor and limbic information within the nucleus accumbens. A dysfunction in the manner by which DA integrates motor and affective states within the nucleus accumbens could provide this affective-motor link unique to TS and obsessive-compulsive disorder. We will study the effects of dopamine-related drugs on the convergence of cortical, hippocampal and amygdaloid inputs on nucleus accumbens neurons intracellularly recorded in vivo. In addition, the effects of dopamine on the hippoc¬ampal gating of cortical throughput in the nucleus accumbens will also be explored in similar experiments. These studies may provide a model of the interactions between motor and limbic systems in the ventral striatum. Our results may prove relevant in understanding the dependence of TS motor symptoms on environmental factors. Patricio O’Donnell, M.D., Ph.D., University of Pittsburgh, Pittsburgh, PA Award $24,931 Tourette Association of America Inc. – Research Grant Award 1996