In this knockin strain, the inserted dominant negative N616R mutation of the NR1 subunit of NMDA receptor (<i>Grin1</i>) is expressed in all brain cells that normally express the dopamine D1 receptor (D1R, <i>Drd1a</i>), including the striatum.  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.  Homozygotes are small and some die prior to weaning. Heterozygous mice are normal in most respects, however they manifest blunted sensitization to cocaine and there are subtle differences in their conditioned place preference to cocaine. 

In this knockin strain, the inserted dominant negative N616R mutation of the NR1 subunit of NMDA receptor (Grin1) is expressed in all brain cells that normally express the dopamine D1 receptor (D1R, Drd1a), including the striatum. 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.

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