Effetti dell'astinenza da morfina in un modello computazionale di un neurone dopaminegico

Dopamine (DA) neurons of the ventral tegmental area (VTA) are involved in the neurobiological mechanisms underlying addictive processes. It has been shown that withdrawal from drugs of abuse, causes profound modifications in the morphology and physiology of these neurons, but the mechanisms underlying these modifications are poorly understood. Because of their high predictive value, computational models are a powerful tool in neurobiological research, and have been 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 from literature, showing how opiate withdrawal-driven morphological and electrophysiological changes could affect the firing rate and pattern of these neurons. The model is composed by 89 membrane segments, with sodium and calcium dynamics responsible for the basal in vivo activity of these neurons; the set of inputs is modeled adding GabaA and AMPA/NMDA synapses, activated in such a way to model the behavior of gabaergic and glutamatergic inputs, respectively. We modeled the opiate withdrawal state by applying to the model morphometric modifications observed experimentally and by modulating the balance of Gaba/Glu inputs as described by electrophysiological data. Our results suggest that changes in the balance of Gaba/Glu inputs could explain the hypofunction of VTA DA neurons with different effects on synaptic efficacy, while morphological changes could be responsible for their higher responsivity to opiate administration observed during opiate withdrawal.