Acute cocaine exposure produces lasting changes in striatal plasticity, but its long‑term effects on glutamate signaling remain unclear. This study examined time‑dependent changes in extracellular glutamate in the rat dorsolateral striatum following a single cocaine injection. In vivo microdialysis revealed a biphasic response, with glutamate levels increasing one day after cocaine exposure and decreasing three and fourteen days later. Mechanistic studies indicate that the initial increase depends on thalamocortical input and is associated with reduced astrocytic markers and glutamate transporter expression, while the later decrease involves altered glutamate transporter activity. These findings demonstrate that a single cocaine exposure causes long‑lasting, pathway‑dependent alterations in striatal glutamate regulation.
