Effects of cocaine exposure on striatal extracellular glutamate and cell surface ionotropic glutamate receptors in low and high cocaine responding rats

Prior studies showed that after withdrawal from repeated cocaine exposure, a cocaine challenge increases striatal extracellular glutamate only in rats that develop locomotor sensitization and sensitized rats exhibit changes in cell surface ionotropic glutamate receptors in nucleus accumbens (NAc). Glutamatergic changes may help to explain why outbred male Sprague‐Dawley rats initially classified as low cocaine responders (LCRs), based on drug‐induced activation, more readily develop cocaine‐induced locomotor sensitization than those classified as high cocaine responders (HCRs). We found increased phosphorylation of striatal NMDA receptor subunit NR2B Y1472 after acute cocaine and AMPA receptor subunit GluR1 Ser845 after repeated cocaine only in LCRs. Using in vivo microdialysis, we uncovered no LCR/HCR differences in extracellular glutamate levels in NAc basally or after acute cocaine (10 mg/kg, i.p.) but plan to investigate glutamate after repeated cocaine. We used Bis(Sulfosuccinimidyl) suberate to examine levels of cell surface AMPA and NMDA receptor subunits in NAc and found no LCR/HCR differences 40 min after 7 days of repeated cocaine. Our results suggest that under the conditions tested neither extracellular glutamate nor cell surface receptor expression underlie initial LCR/HCR classification or LCR sensitization, respectively. Supported by DA027277, DA004216, GM007635, DA015050.