Dopaminergic Neurons in the Ventral Tegmental Area and Their Dysregulation in Nicotine Addiction

Abstract Nicotine is widely considered the major addictive substance in tobacco. While the receptor mechanisms of nicotine have been identified, the circuit level mechanisms by which it usurps dopamine signaling are still not completely clear. In this chapter we describe two modeling approaches: the first is a receptor-circuit model of the ventral tegmental area (VTA), the second is a more detailed modeling of dopamine neuron spiking. Using the circuit model we show that nicotine-evoked upregulation of receptors on the VTA γ -amino butyric acid neurons is a sufficient mechanism for alterations in dopaminergic signaling. Crucially the model points out how nicotine may act to renormalize the otherwise pathological dopamine circuitry in individuals with substance use disorders. In the second approach we show that nicotine-driven increases in glutamate input synchrony to the dopamine neurons induce bursting and hence increased phasic dopamine release. We discuss open questions and ways for models to delineate the mechanisms of nicotine control over motivational signals in the brain.