Cocaine effects on dopamine and NMDA receptors interactions in the striatum of Fischer rats.

Numerous studies have shown that biochemical and behavioral effects of cocaine are mediated by dopamine D1 receptor (D1R) and NMDA R1 receptor (NR1)-mediated transmission. In this study, we investigated the physical interactions between D1R and NR1 in response to acute cocaine administration in a time course of 5-60 min. In the caudate-putamen (CPu) of male Fischer rats, a single cocaine injection (30 mg/kg) reduced D1R-NR1 protein-protein interactions 30 min after treatment. In addition, activation or blockade of the NMDA receptor using NMDA (25mg/kg) or MK-801 (0.25mg/kg), respectively, also reduced the D1R-NR1 physical interactions. Acute cocaine administration did not alter total D1R or NR1 protein levels in our time course of study. These results indicate that D1R-NR1 physical interaction rather than total protein levels may regulate the intracellular signaling after acute cocaine administration.