RESUMO
Case reports indicate that deep-brain stimulation in the nucleus accumbens may be beneficial to alcohol-dependent patients. The lack of clinical trials and our limited knowledge of deep-brain stimulation call for translational experiments to validate these reports. To mimic the human situation, we used a chronic-continuous brain-stimulation paradigm targeting the nucleus accumbens and other brain sites in alcohol-dependent rats. To determine the network effects of deep-brain stimulation in alcohol-dependent rats, we combined electrical stimulation of the nucleus accumbens with functional magnetic resonance imaging (fMRI), and studied neurotransmitter levels in nucleus accumbens-stimulated versus sham-stimulated rats. Surprisingly, we report here that electrical stimulation of the nucleus accumbens led to augmented relapse behavior in alcohol-dependent rats. Our associated fMRI data revealed some activated areas, including the medial prefrontal cortex and caudate putamen. However, when we applied stimulation to these areas, relapse behavior was not affected, confirming that the nucleus accumbens is critical for generating this paradoxical effect. Neurochemical analysis of the major activated brain sites of the network revealed that the effect of stimulation may depend on accumbal dopamine levels. This was supported by the finding that brain-stimulation-treated rats exhibited augmented alcohol-induced dopamine release compared with sham-stimulated animals. Our data suggest that deep-brain stimulation in the nucleus accumbens enhances alcohol-liking probably via augmented dopamine release and can thereby promote relapse.
Assuntos
Alcoolismo/fisiopatologia , Estimulação Encefálica Profunda , Núcleo Accumbens/fisiopatologia , Animais , Núcleo Caudado/fisiopatologia , Modelos Animais de Doenças , Dopamina/metabolismo , Imageamento por Ressonância Magnética , Masculino , Córtex Pré-Frontal/fisiopatologia , Putamen/fisiopatologia , Ratos , Ratos Wistar , RecidivaRESUMO
The effects of the acute ethanol consumption on the brain's neurochemistry are largely studied at the synaptic level. Here, the acute action of low dosages of ethanol, in terms of the inhibition of the glutamatergic system through antagonizing the N-methyl-D-aspartate receptors, on the neurochemical oscillations along the neurocircuitry of the basal ganglia is investigated by mathematical models. Substantial alterations in the dynamical behaviour of the neurochemical oscillations after single administration of low dosages of ethanol have been observed. Significant dynamical changes in the gamma-aminobutyric acid and glutamate systems along the subthalamic-pallidal feedback loop and the dopamine system of the striatal complex suggest new perspectives in the understanding of the ethanol-induced motor dysfunctions.
Assuntos
Gânglios da Base/efeitos dos fármacos , Etanol/farmacologia , Modelos Neurológicos , Receptores de N-Metil-D-Aspartato/metabolismo , Gânglios da Base/metabolismo , Relógios Biológicos/efeitos dos fármacos , Simulação por Computador , Humanos , Receptores de N-Metil-D-Aspartato/antagonistas & inibidoresRESUMO
Astrocytes play a critical role in CNS metabolism, regulation of volume and ion homeostasis of the interstitial space. Of special relevance is their clearance of K(+) that is released by active neurons into the extracellular space. Mathematical analysis of a modified Nernst equation for the electrochemical equilibrium of neuronal plasma membranes, suggests that K(+) uptake by glial cells is not only relevant during neuronal activity but also has a non-neglectable impact on the basic electrical membrane properties, specifically the resting membrane potential, of neurons and might be clinically valuable as a factor in the genetics and epigenetics of the epilepsy and tuberous sclerosis complex.
