First Author | Zweifel LS | Year | 2008 |
Journal | Neuron | Volume | 59 |
Issue | 3 | Pages | 486-96 |
PubMed ID | 18701073 | Mgi Jnum | J:145468 |
Mgi Id | MGI:3834789 | Doi | 10.1016/j.neuron.2008.05.028 |
Citation | Zweifel LS, et al. (2008) Role of NMDA receptors in dopamine neurons for plasticity and addictive behaviors. Neuron 59(3):486-96 |
abstractText | A 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. |