Cocaine-induced adaptations in D1 and D2 accumbens projection neurons (a dichotomy not necessarily synonymous with direct and indirect pathways)

Cocaine exposure causes enduring neuroadaptations in ventral striatum, or nucleus accumbens (NAc), an area critically involved in reward learning and relapse of drug seeking. Medium spiny neurons (MSNs) in striatum are dichotomous in their expression of either D1 or D2 dopamine receptors, along with other receptors and neuropeptides. In dorsal striatum, these two subpopulations show non-overlapping innervation of distinct terminal fields via the direct or indirect pathways. However, NAc D1-MSNs and D2-MSNs are not fully segregated in this manner, with both cell types innervating ventral pallidum. Recent studies show that D1-MSNs and D2-MSNs play opposing roles in cocaine-associated behaviors. Further, cocaine induces differential adaptations in these two subpopulations in NAc, including changes to synaptic plasticity, glutamatergic signaling, and spine morphology.

► Cocaine-induced adaptations in nucleus accumbens (NAc) contribute to relapse. ► Projection neurons in NAc are D1 or D2 dopamine receptor-expressing. ► D1 and D2 cell types in NAc are not synonymous with direct/indirect pathways. ► NAc neurons show cocaine-induced changes in synaptic plasticity. ► New technologies examine involvement of D1 and/or D2 projection neurons.