Modelling the nicotinic control of dopamine release
Dr. Reinoud Maex
The dopaminergic and cholinergic systems closely interact in the basal ganglia, and their integrity is affected in diseases such as Parkinson's and Alzheimer's, schizophrenia and addiction. We constructed models of the nicotinic receptors and the circuit that are involved in the control of dopamine release, and show how pharmacological compounds may alter the dynamics of this circuit through receptor desensitization, upregulation, or sensitization. We present three cases to illustrate this plastic effect of exogenous compounds. In the first study, it is shown how nicotinic partial agonists can acutely depress dopamine release through receptor desensitization. In the second example, the model shows how nicotine may enhance dopamine release in nicotine abusers despite the chronic upregulation of nicotinic receptors on the GABAergic interneurons. The third case explains the dyskinesias that appear in Parkinson patients, after years of levo-dopa treatment, from a supersensitivity of the dopamine receptors on the cholinergic interneurons.