Endogenous Dopamine and Endocannabinoid Signaling Mediate Cocaine-Induced Reversal of AMPAR Synaptic Potentiation in the Nucleus Accumbens Shell

Authors

Anna E. Ingebretson, University of Minnesota
Matthew C. Hearing, Marquette UniversityFollow
Ethan D. Huffington, University of Minnesota
Mark J. Thomas, University of Minnesota

Document Type

Article

Publication Date

3-15-2018

Publisher

Elsevier

Source Publication

Neuropharmacology

Source ISSN

0028-3908

Original Item ID

DOI: 10.1016/j.neuropharm.2017.12.011

Abstract

Repeated exposure to drugs of abuse alters the structure and function of neural circuits mediating reward, generating maladaptive plasticity in circuits critical for motivated behavior. Within meso-corticolimbic dopamine circuitry, repeated exposure to cocaine induces progressive alterations in AMPAR-mediated glutamatergic synaptic transmission. During a 10–14 day period of abstinence from cocaine, AMPAR signaling is potentiated at synapses on nucleus accumbens (NAc) medium spiny neurons (MSNs), promoting a state of heightened synaptic excitability. Re-exposure to cocaine during abstinence, however, rapidly reverses and depotentiates enhanced AMPAR signaling. To understand how re-exposure to cocaine alters AMPAR synaptic transmission, we investigated the roles of dopamine and endocannabinoid (eCB) signaling in modifying synaptic strength in the NAc shell. Using patch-clamp recordings from NAc slices prepared after 10–14 days of abstinence from repeated cocaine, we found that AMPAR-mediated depotentiation is rapidly induced in the NAc shell within 20 min of cocaine re-exposure ex vivo, and persists for up to five days before synapses return to levels of potentiation observed during abstinence. In cocaine-treated animals, global dopamine receptor activation was both necessary and sufficient for the cocaine-evoked depotentiation of AMPAR synaptic function. Additionally, we identified that CB1 receptors are engaged by endogenous endocannabinoids (eCBs) during re-exposure to cocaine ex vivo. Overall, these results indicate the central role that dopamine and eCB signaling mechanisms play in modulating cocaine-induced AMPAR plasticity in the NAc shell.

Comments

Accepted version. Neuropharmacology, Vol. 131 (March 15, 2018): 154-165. DOI. © 2018 Elsevier B.V. Used with permission.

Recommended Citation

Ingebretson, Anna E.; Hearing, Matthew C.; Huffington, Ethan D.; and Thomas, Mark J., "Endogenous Dopamine and Endocannabinoid Signaling Mediate Cocaine-Induced Reversal of AMPAR Synaptic Potentiation in the Nucleus Accumbens Shell" (2018). Biomedical Sciences Faculty Research and Publications. 211.
https://epublications.marquette.edu/biomedsci_fac/211