Chunk #22 — Results — Widespread effects of cocaine and withdrawal on catecholaminergic, GABAergic, cholinergic, glutamatergic, and endocannabinoid pathways
Glutamatergic signaling plays an essential role in drug abuse, with major glutamatergic inputs onto NAc medium spiny neurons (MSNs) coming from amygdala, hippocampus, and prefrontal cortex (Kalivas, 2009; Wolf, 2010). The effects of cocaine on expression of ionotropic and metabotropic glutamate receptors have been studied in detail (Kalivas, 2009; Kalivas et al., 2009; Kalivas and Volkow, 2011) and were largely confirmed in our analysis (Figure 6). Glutamatergic inputs acutely excite NAc MSNs primarily via activation of AMPA receptors, a step considered necessary for initiation of drug seeking behavior (Wolf and Ferrario, 2010). AMPA receptor expression showed only small changes during Cocaine administration; Gria1 increased substantially while Gria3 decreased during Withdrawal (confirmed by qPCR). Expression of several NMDA receptor subunits increased during Cocaine administration (Grin1, Grin2a, Grin2b, Grin2d, Grin3a) (several confirmed by qPCR). Expression of kainate receptors Grik1, Grik2, and Grik3 showed a sustained increase while expression of Grik4 and Grik5 showed a sustained decrease. Expression of the five most-highly expressed metabotropic receptors for glutamate (Grm1, Grm3, Grm4, Grm5, and Grm7) showed a sustained increase. Vesicular glutamate transporters (Vglut) can be
