Cocaine preference and neuroadaptations are maintained by astrocytic NMDA receptors in the nucleus accumbens

• DOI: 10.1126/sciadv.abo6574
• Publication Date: 2022-07-22T17:58:21Z
• Authors: Gajanan P. Shelkar; Pauravi J. Gandhi; Jinxu Liu; Shashank M. Dravid
• Keywords: Conditioned place preference; Extinction (optical mineralogy); Medium spiny neuron; Knockout mouse

Cocaine-associated memories induce cravings and interfere with the ability of users to cease cocaine use. Reducing strength cue-drug by facilitating extinction may have therapeutic value for treatment addiction. Here, we demonstrate expression GluN1/2A/2C NMDA receptor currents in astrocytes nucleus accumbens core. Selective ablation GluN1 subunit from enhanced preference memory but did not affect conditioning or reinstatement. Repeated exposure up-regulated GluN2C increased astrocytic currents. Furthermore, intra-accumbal inhibition GluN2C/2D-containing receptors deletion facilitated memory. Cocaine-induced neuroadaptations including dendritic spine maturation AMPA recruitment were absent knockout mice. Impaired retention mice was restored exogenous administration recombinant glypican 4. Together, these results identify a previously unknown GluN2C-containing mechanism underlying maintenance