Brief ReportN-Methyl-D-Aspartic Acid Receptors on Striatal Neurons Are Essential for Cocaine Cue Reactivity in Mice
Section snippets
Animals
Adult male conditional NMDAR KO (RGS9-cre/NR1flox/flox) and control (NR1flox/flox) mice were used in this study. These strains of mice have been used in a previous study (13). Mice were maintained under a 14-hour light/10-hour dark cycle with food and water available ad libitum. Animal handling and use procedures followed a protocol approved by the Animal Care and Use Committee of Albert Einstein College of Medicine, in accordance with National Institutes of Health guidelines.
Drugs
Cocaine
Results
Neither control nor KO mice showed a preconditioning bias to either compartment [Figure 1A; Genotype, F(1,25) = 1.79, NS; Compartment, F(1,25) = 1.65, NS; genotype × compartment, F(1,25) = .04, NS]. The CPP scores on the postconditioning test day showed a significant interaction between Genotype and Compartment [F(1,23) = 5.89, p = .024.]. Exploratory ANOVAs showed that CPP was abolished in KO mice [Dose, F(1,14) = 1.39, NS; Compartment, F(1,14) = .002, NS; dose × compartment, F(1,14) = .004,
Discussion
We assessed the role of NMDAR on striatal neurons in cue reactivity, an element of cocaine addiction, in the place conditioning paradigm. Our results show that mice deficient in NMDAR on striatal neurons failed to show cocaine CPP.
In the conditional KO mice, the excision of NMDAR was restricted by RGS9-dependent Cre expression (13). The RGS9 messenger RNA is expressed in striatal cholinergic interneurons, the striatal indirect pathway projecting to the external segment of the pallidum, and the
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