RESUMEN
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.
Asunto(s)
Simulación por Computador , Neuronas Dopaminérgicas/fisiología , Modelos Neurológicos , Trastornos Relacionados con Opioides/fisiopatología , Síndrome de Abstinencia a Sustancias/fisiopatología , Área Tegmental Ventral/fisiopatología , Potenciales de Acción/efectos de los fármacos , Animales , Neuronas Dopaminérgicas/efectos de los fármacos , Neuronas Dopaminérgicas/patología , Conductividad Eléctrica , Narcóticos/toxicidad , Alcaloides Opiáceos/toxicidad , Trastornos Relacionados con Opioides/patología , Receptores de GABA-A/metabolismo , Síndrome de Abstinencia a Sustancias/patología , Área Tegmental Ventral/efectos de los fármacos , Área Tegmental Ventral/patologíaRESUMEN
The thymus of rats of ages between 1 and 7 months was homogenised and subjected to oxidative stress induced by iron salts. Lipid peroxidation, protein thiols and glutathione status were evaluated. The thymus of rats of 1 month of age exhibited lower susceptibility to the radical attack with respect to the thymus of rats between 3 and 7 months of age. This susceptibility was correlated with the content of polyunsaturated fatty acids and of lipophylic chain-breaking antioxidants.