Drug-evoked plasticity at excitatory synapses on medium spiny neurons (MSNs) of the nucleus accumbens (NAc) drives behavioral adaptations in addiction. MSNs expressing dopamine D1 (D1R-MSN) vs. D2 receptors (D2R-MSN) can exert antagonistic effects in drugrelated behaviors, and display distinct alterations in glutamate signaling following repeated exposure to psychostimulants; however, little is known of cell-type-specific plasticity induced by opiates. Here, we find that repeated morphine potentiates excitatory transmission and increases GluA2-lacking AMPA receptor expression in D1R-MSNs, while reducing signaling in D2-MSNs following 10-14 d of forced abstinence. In vivo reversal of this pathophysiology with optogenetic stimulation of infralimbic cortexaccumbens shell (ILC-NAc shell) inputs or treatment with the antibiotic, ceftriaxone, blocked reinstatement of morphine-evoked conditioned place preference. These findings confirm the presence of overlapping and distinct plasticity produced by classes of abused drugs within subpopulations of MSNs that may provide targetable molecular mechanisms for future pharmacotherapies.
|Original language||English (US)|
|Number of pages||6|
|Journal||Proceedings of the National Academy of Sciences of the United States of America|
|State||Published - Jan 19 2016|
Bibliographical noteFunding Information:
The MnDRIVE Optogenetics Core at the University of Minnesota provided invaluable technical support. This work was supported by funding from the National Institute on Drug Abuse Grants R01 DA019666, K02 DA035459 (to M.J.T.), K99 DA038706 (to M.C.H.), and T32 DA007234 (to A.I. and S.R.E.); the MnDRIVE Initiative on Brain Conditions; and the Breyer-Longden Family Research Fund.
- Glua2-lacking AMPARs
- Nucleus accumbens