Up-regulation of dopamine D1 receptor in the hippocampus after establishment of conditioned place preference by cocaine

The hippocampus plays an important role in the formation of contextual memory between the environment and the rewarding effect of abused drugs. The dopaminergic neural transmission in the hippocampus seems to be critical for such memory. Using conditioned place preference in rats, we found that the protein level of the dopamine D1 receptor and its prerequisite mRNA in the hippocampus increased in animals that showed a clear preference for the environment paired with cocaine. The increase was not a simple reflection of the repeated administration of cocaine. Instead, it is attributable to conditioning, because systematic contingency between drug administration and exposure to a particular environment was necessary for the increase. Furthermore, we found that the mRNA of the dopamine D1 receptors increased in the granule cell layer of the dentate gyrus. These results suggest that the alteration of dopamine D1 receptor in the hippocampus, especially in the dentate gyrus, is related to the induction of drug-induced contextual memory. The finding implicates the relevance of the dopaminergic signal transduction in the hippocampus to drug dependence.

► The protein levels of D1R increased in the hippocampus of animals showing cocaine-induced CPP.
► The mRNA levels of D1R also increased in the hippocampus of animals showing cocaine-induced CPP.
► Augmentation of the D1R mRNA was detected in the granular cellular layer of the DG of animals showing cocaine-induced CPP.