1. Role of NMDA Receptors in Dopamine Neurons for Plasticity and Addictive Behaviors
- Author
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Emanuela Argilli, Richard D. Palmiter, Antonello Bonci, and Larry S. Zweifel
- Subjects
Patch-Clamp Techniques ,Dopamine ,HUMDISEASE ,Pharmacology ,Membrane Potentials ,Mice ,0302 clinical medicine ,Cocaine ,Sensitization ,media_common ,Neurons ,0303 health sciences ,Neuronal Plasticity ,Behavior, Animal ,musculoskeletal, neural, and ocular physiology ,General Neuroscience ,Long-term potentiation ,3. Good health ,Ventral tegmental area ,medicine.anatomical_structure ,NMDA receptor ,Psychology ,Locomotion ,medicine.drug ,N-Methylaspartate ,Tyrosine 3-Monooxygenase ,Neuroscience(all) ,media_common.quotation_subject ,Mice, Transgenic ,Nerve Tissue Proteins ,AMPA receptor ,In Vitro Techniques ,Receptors, N-Methyl-D-Aspartate ,Article ,03 medical and health sciences ,mental disorders ,Neuroplasticity ,medicine ,Animals ,alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid ,030304 developmental biology ,Dopamine Plasma Membrane Transport Proteins ,Addiction ,Ventral Tegmental Area ,Behavior, Addictive ,Luminescent Proteins ,nervous system ,Exploratory Behavior ,SYSNEURO ,Carrier Proteins ,Neuroscience ,Psychomotor Performance ,030217 neurology & neurosurgery - Abstract
SummaryA single exposure to drugs of abuse produces an NMDA receptor (NMDAR)-dependent long-term potentiation (LTP) of AMPA receptor (AMPAR) currents in DA neurons; however, the importance of LTP for various aspects of drug addiction is unclear. To test the role of NMDAR-dependent plasticity in addictive behavior, we genetically inactivated functional NMDAR signaling exclusively in DA neurons (KO mice). Inactivation of NMDARs results in increased AMPAR-mediated transmission that is indistinguishable from the increases associated with a single cocaine exposure, yet locomotor responses to multiple drugs of abuse were unaltered in the KO mice. The initial phase of locomotor sensitization to cocaine is intact; however, the delayed sensitization that occurs with prolonged cocaine withdrawal did not occur. Conditioned behavioral responses for cocaine-testing environment were also absent in the KO mice. These findings provide evidence for a role of NMDAR signaling in DA neurons for specific behavioral modifications associated with drug seeking behaviors.
- Published
- 2008
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