期刊
JOURNAL OF NEUROSCIENCE
卷 25, 期 28, 页码 6651-6657出版社
SOC NEUROSCIENCE
DOI: 10.1523/JNEUROSCI.1474-05.2005
关键词
dopamine; NMDA receptor; conditioned place preference; cocaine; sensitization; transgenic
资金
- NIDA NIH HHS [T32-DA07278, T32 DA007278] Funding Source: Medline
The interaction of dopamine and glutamate in limbic brain regions mediates behaviors associated with psychostimulants, which act in part to increase dopamine signaling at both D-1 receptors (D1Rs) and D-2 receptors. Many addictive behaviors are a result of learned associations, and NMDA receptor activation has been shown to be important for these behaviors. We hypothesized that if NMDA receptor activation in dopamine receptor-containing cells is required for the addictive properties of psychostimulants, then mice with reduced NMDA receptor activity in D1R-containing cells would have attenuated long-term behavioral changes to these drugs. We generated a mouse line in which D1R-containing cells express an NR1 NMDA receptor subunit containing a mutation in the pore that reduces calcium flux. Mice expressing the mutant NMDA receptors in D1R-containing cells have normal basal activity and display similar increases in locomotor activity when treated with acute amphetamine or cocaine. However, the mutant mice fail to display locomotor sensitization to repeated cocaine administration. In addition, these mice also have a decreased ability to form a conditioned place preference to cocaine. These data suggest that intact NMDA receptor signaling in D1R-containing cells is required for the manifestation of behaviors associated with repeated drug exposure.
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