DARPP-32 and regulation of the ethanol sensitivity of NMDA receptors in the nucleus accumbens
| Autor: | Regina E. Maldve, Rueben A. Gonzales, Tao A. Zhang, K. Ferrani-Kile, Steven W. Leslie, Allen A. Fienberg, Richard A. Morrisett, G. L. Snyder, Melanie J. Lippmann, S. S. Schreiber |
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| Rok vydání: | 2002 |
| Předmět: |
Dopamine and cAMP-Regulated Phosphoprotein 32
Dopamine Nerve Tissue Proteins In Vitro Techniques Nucleus accumbens Medium spiny neuron Receptors N-Methyl-D-Aspartate Nucleus Accumbens Mice Cyclic AMP medicine Animals Phosphorylation Long-term depression Mice Knockout Neuronal Plasticity Ethanol Chemistry Receptors Dopamine D1 General Neuroscience Ventral Tegmental Area Dopaminergic Phosphoproteins Cyclic AMP-Dependent Protein Kinases Rats Ventral tegmental area medicine.anatomical_structure nervous system Dopamine Agonists Synaptic plasticity NMDA receptor 2 3 4 5-Tetrahydro-7 8-dihydroxy-1-phenyl-1H-3-benzazepine Neuroscience medicine.drug |
| Zdroj: | Nature Neuroscience. 5:641-648 |
| ISSN: | 1546-1726 1097-6256 |
| DOI: | 10.1038/nn877 |
| Popis: | The medium spiny neurons of the nucleus accumbens receive both an excitatory glutamatergic input from forebrain and a dopaminergic input from the ventral tegmental area. This integration point may constitute a locus whereby the N-methyl-D-aspartate (NMDA)-subtype of glutamate receptors promotes drug reinforcement. Here we investigate how dopaminergic inputs alter the ethanol sensitivity of NMDA receptors in rats and mice and report that previous dopamine receptor-1 (D1) activation, culminating in dopamine and cAMP-regulated phosphoprotein-32 kD (DARPP-32) and NMDA receptor subunit-1 (NR1)-NMDA receptor phosphorylation, strongly decreases ethanol inhibition of NMDA responses. The regulation of ethanol sensitivity of NMDA receptors by D1 receptors was absent in DARPP-32 knockout mice. We propose that DARPP-32 mediated blunting of the response to ethanol subsequent to activation of ventral tegmental area dopaminergic neurons initiates molecular alterations that influence synaptic plasticity in this circuit, thereby promoting the development of ethanol reinforcement. |
| Databáze: | OpenAIRE |
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