Genetic loss of GluN2B in D1-expressing cell types enhances long-term cocaine reward and potentiation of thalamo-accumbens synapses.

Joffe ME, Turner BD, Delpire E, Grueter BA
Neuropsychopharmacology. 2018 43 (12): 2383-2389

PMID: 29982266 · PMCID: PMC6180117 · DOI:10.1038/s41386-018-0131-8

Transient upregulation of GluN2B-containing NMDA receptors (R) in the nucleus accumbens (NAc) is proposed as an intermediate to long-term AMPAR plasticity associated with persistent cocaine-related behaviors. However, cell type- and input-specific contributions of GluN2B underlying lasting actions of cocaine remain to be elucidated. We utilized GluN2B cell type-specific knockouts and optogenetics to deconstruct the role of GluN2B in cocaine-induced NAc synaptic and behavioral plasticity. While reward learning was unaffected, loss of GluN2B in D1 dopamine receptor-expressing cells (D1) led to prolonged retention of reward memory. In control mice, prefrontal cortex (PFC)-D1(+) NAc AMPAR function was unaffected by cocaine exposure, while midline thalamus (mThal)-D1(+) NAc AMPAR function was potentiated but diminished after withdrawal. In D1-GluN2B mice, the potentiation of mThal-D1(+) NAc AMPAR function persisted following withdrawal, corresponding with continued expression of cocaine reward behavior. These data suggest NAc GluN2B-containing NMDARs serve a feedback role and may weaken reward-related memories.

MeSH Terms (13)

Animals Cocaine Gene Deletion Locomotion Male Mice Mice, Inbred C57BL Mice, Transgenic Nucleus Accumbens Receptors, Dopamine D1 Receptors, N-Methyl-D-Aspartate Reward Thalamus

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