title: Morphofunctional alterations in ventral tegmental area dopamine neurons in acute and prolonged opiates withdrawal. A computational perspective.
abstract: 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 acute and long-term 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 opiates withdrawal-driven morphological and electrophysiological changes could affect the firing rate and discharge pattern. The model findings suggest how and to what extent a change in the balance of GABA/GLU inputs can take into account the experimentally observed hypofunction of VTA DA neurons during acute and prolonged withdrawal, whereas morphological changes may play a role in the increased excitability of VTA DA cell to opiate administration observed during opiate withdrawal.
authors.affiliation: Department of Biomedical Sciences, University of Sassari, V.le S. Pietro 43/B, Sassari 07100, Italy. Electronic address: enrico@uniss.it.
authors.forename: P
authors.initials: P
authors.lastname: Enrico
authors.affiliation: Institute of Biophysics, National Research Council, Via U. La Malfa 153, Palermo 90146, Italy.
authors.forename: M
authors.initials: M
authors.lastname: Migliore
authors.affiliation: Department of Life and Environmental Sciences, University of Cagliari, V.le S. Ignazio da Laconi 13, Cagliari 09123, Italy.
authors.forename: S
authors.initials: S
authors.lastname: Spiga
authors.affiliation: Department of Life and Environmental Sciences, University of Cagliari, V.le S. Ignazio da Laconi 13, Cagliari 09123, Italy.
authors.forename: G
authors.initials: G
authors.lastname: Mulas
authors.affiliation: Department of Life and Environmental Sciences, University of Cagliari, V.le S. Ignazio da Laconi 13, Cagliari 09123, Italy.
authors.forename: F
authors.initials: F
authors.lastname: Caboni
authors.affiliation: Department of Chemistry and Pharmacy, Laboratory of Cognitive Neuroscience, University of Sassari, Via Vienna 2, Sassari 07100, Italy.
authors.forename: M
authors.initials: M
authors.lastname: Diana
mesh_terms: D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D003198:Computer Simulation; D059290:Dopaminergic Neurons / Q000187:drug effects / Q000473:pathology / Q000502:physiology*; D004553:Electric Conductivity; D008959:Models, Neurological; D009294:Narcotics / Q000633:toxicity; D053610:Opiate Alkaloids / Q000633:toxicity; D009293:Opioid-Related Disorders / Q000473:pathology / Q000503:physiopathology*; D011963:Receptors, GABA-A / Q000378:metabolism; D013375:Substance Withdrawal Syndrome / Q000473:pathology / Q000503:physiopathology*; D017557:Ventral Tegmental Area / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology*
chemical_list: D009294:Narcotics; D053610:Opiate Alkaloids; D011963:Receptors, GABA-A
keywords: GABA; NEURON simulator; glutamate; opiate withdrawal; ventral tegmental area dopamine