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GABA Neurons (gaba + neuron)

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Medical Sciences100%

Selected Abstracts

Acute and Chronic Ethanol Modulate Dopamine D2-Subtype Receptor Responses in Ventral Tegmental Area GABA Neurons

ALCOHOLISM, Issue 5 2009
Kimberly H. Ludlow
Background:, Ventral tegmental area (VTA) ,-aminobutyric acid (GABA) neurons appear to be critical substrates underlying the acute and chronic effects of ethanol on dopamine (DA) neurotransmission in the mesocorticolimbic system implicated in drug reward. VTA GABA neuron firing rate is reduced by acute ethanol and enhanced by DA via D2 receptor activation. The objective of this study was to evaluate the role of D2 receptors in acute ethanol inhibition of VTA GABA neuron activity, as well as the adaptation of D2 receptors by chronic ethanol consumption. Methods:, Using electrophysiological methods, we evaluated the effects of intraperitoneal ethanol on DA activation of VTA GABA neurons, the effects of DA antagonists on ethanol inhibition of their firing rate, as well as adaptations in firing rate following chronic ethanol consumption. Using single cell quantitative RT-polymerase chain reaction (PCR), we evaluated the expression of VTA GABA neuron D2 receptors in rats consuming ethanol versus pair-fed controls. Results:, In acute ethanol studies, microelectrophoretic activation of VTA GABA neurons by DA was inhibited by acute intraperitoneal ethanol, and intravenous administration of the D2 antagonist eticlopride blocked ethanol suppression of VTA GABA neuron firing rate. In chronic ethanol studies, while there were no signs of withdrawal at 24 hours, or significant adaptation in firing rate or response to acute ethanol, there was a significant down-regulation in the expression of D2 receptors in ethanol-consuming rats versus pair-fed controls. Conclusions:, Inhibition of DA activation of VTA GABA neuron firing rate by ethanol, as well as eticlopride block of ethanol inhibition of VTA GABA neuron firing rate, suggests an interaction between ethanol and DA neurotransmission via D2 receptors, perhaps via enhanced DA release in the VTA subsequent to ethanol inhibition of GABA neurons. Down-regulation of VTA GABA neuron D2 receptors by chronic ethanol might result from persistent DA release onto GABA neurons. [source]

Adenosine A2A receptors, dopamine D2 receptors and their interactions in Parkinson's disease

MOVEMENT DISORDERS, Issue 14 2007
Kjell Fuxe MD
Abstract Future therapies in Parkinson's disease may substantially build on the existence of intra-membrane receptor,receptor interactions in DA receptor containing heteromeric receptor complexes. The A2A/D2 heteromer is of substantial interest in view of its specific location in cortico-striatal glutamate terminals and in striato-pallidal GABA neurons. Antagonistic A2A/D2 receptor interactions in this heteromer demonstrated at the cellular level, and at the level of the striato-pallidal GABA neuron and at the network level made it possible to suggest A2A antagonists as anti-parkinsonian drugs. The major mechanism is an enhancement of D2 signaling leading to attenuation of hypokinesia, tremor, and rigidity in models of Parkinson's disease with inspiring results in two clinical trials. Other interactions are antagonism at the level of the adenylyl cyclase; heterologous sensitization at the A2A activated adenylyl cyclase by persistent D2 activation and a compensatory up-regulation of A2A receptors in response to intermittent Levodopa treatment. An increased dominance of A2A homomers over D2 homomers and A2A/D2 heteromers after intermittent Levodopa treatment may therefore contribute to development of Levodopa induced dyskinesias and to the wearing off of the therapeutic actions of Levodopa giving additional therapeutic roles of A2A antagonists. Their neuroprotective actions may involve an increase in the retrograde trophic signaling in the nigro-striatal DA system. © 2007 Movement Disorder Society [source]

Acute and Chronic Ethanol Modulate Dopamine D2-Subtype Receptor Responses in Ventral Tegmental Area GABA Neurons

ALCOHOLISM, Issue 5 2009
Kimberly H. Ludlow
Background:, Ventral tegmental area (VTA) ,-aminobutyric acid (GABA) neurons appear to be critical substrates underlying the acute and chronic effects of ethanol on dopamine (DA) neurotransmission in the mesocorticolimbic system implicated in drug reward. VTA GABA neuron firing rate is reduced by acute ethanol and enhanced by DA via D2 receptor activation. The objective of this study was to evaluate the role of D2 receptors in acute ethanol inhibition of VTA GABA neuron activity, as well as the adaptation of D2 receptors by chronic ethanol consumption. Methods:, Using electrophysiological methods, we evaluated the effects of intraperitoneal ethanol on DA activation of VTA GABA neurons, the effects of DA antagonists on ethanol inhibition of their firing rate, as well as adaptations in firing rate following chronic ethanol consumption. Using single cell quantitative RT-polymerase chain reaction (PCR), we evaluated the expression of VTA GABA neuron D2 receptors in rats consuming ethanol versus pair-fed controls. Results:, In acute ethanol studies, microelectrophoretic activation of VTA GABA neurons by DA was inhibited by acute intraperitoneal ethanol, and intravenous administration of the D2 antagonist eticlopride blocked ethanol suppression of VTA GABA neuron firing rate. In chronic ethanol studies, while there were no signs of withdrawal at 24 hours, or significant adaptation in firing rate or response to acute ethanol, there was a significant down-regulation in the expression of D2 receptors in ethanol-consuming rats versus pair-fed controls. Conclusions:, Inhibition of DA activation of VTA GABA neuron firing rate by ethanol, as well as eticlopride block of ethanol inhibition of VTA GABA neuron firing rate, suggests an interaction between ethanol and DA neurotransmission via D2 receptors, perhaps via enhanced DA release in the VTA subsequent to ethanol inhibition of GABA neurons. Down-regulation of VTA GABA neuron D2 receptors by chronic ethanol might result from persistent DA release onto GABA neurons. [source]

Adenosine A2A receptors, dopamine D2 receptors and their interactions in Parkinson's disease

MOVEMENT DISORDERS, Issue 14 2007
Kjell Fuxe MD
Abstract Future therapies in Parkinson's disease may substantially build on the existence of intra-membrane receptor,receptor interactions in DA receptor containing heteromeric receptor complexes. The A2A/D2 heteromer is of substantial interest in view of its specific location in cortico-striatal glutamate terminals and in striato-pallidal GABA neurons. Antagonistic A2A/D2 receptor interactions in this heteromer demonstrated at the cellular level, and at the level of the striato-pallidal GABA neuron and at the network level made it possible to suggest A2A antagonists as anti-parkinsonian drugs. The major mechanism is an enhancement of D2 signaling leading to attenuation of hypokinesia, tremor, and rigidity in models of Parkinson's disease with inspiring results in two clinical trials. Other interactions are antagonism at the level of the adenylyl cyclase; heterologous sensitization at the A2A activated adenylyl cyclase by persistent D2 activation and a compensatory up-regulation of A2A receptors in response to intermittent Levodopa treatment. An increased dominance of A2A homomers over D2 homomers and A2A/D2 heteromers after intermittent Levodopa treatment may therefore contribute to development of Levodopa induced dyskinesias and to the wearing off of the therapeutic actions of Levodopa giving additional therapeutic roles of A2A antagonists. Their neuroprotective actions may involve an increase in the retrograde trophic signaling in the nigro-striatal DA system. © 2007 Movement Disorder Society [source]