Ventral Tegmental Area dopamine neurons in opiate withdrawal: a computational perspective.

Dopamine (DA) neurons of the ventral tegmental area (VTA) play a key role in the neurobiological basis of goal-directed behaviors and addiction. Morphine (MOR) withdrawal induces profound changes in the morphology and physiology of VTA DA cells, but the mechanisms underlying these modifications are poorly understood. Because of their predictive value, computational models are a powerful tool in neurobiological research, and are often used to gain further insights and deeper understanding on the molecular and physiological mechanisms underlying the development of various psychiatric disorders. Here we present a biophysical model of a DA VTA neuron based on 3D morphological reconstruction and electrophysiological data, showing how opiate withdrawal-driven morphological and electrophysiological changes could affect the firing rate and discharge pattern. The model findings suggest that changes in the balance of GABA/GLU inputs could explain the experimentally observed hypofunction of VTA DA neurons, while morphological changes could be responsible for their higher responsiveness to opiate administration observed during opiate withdrawal.