NMDA receptor antagonists prevent conditioned activation of intracranial self-stimulation in rats.

Rats with bipolar electrodes implanted unilaterally into the ventral tegmental area were trained to lever-press for response contingent electrical stimulation (continuous reinforcement). After preliminary lever-press training, two types of daily sessions were held on 10 consecutive days: type T+, during which current intensity was set at the Threshold level and each response was accompanied by the visual signal (stimulus lights above the lever briefly went off); and type ST-, during which current was set at the SubThreshold level and there were no visual stimuli. On day 11, combination of the subthreshold current intensities and stimulus lights previously associated with the threshold stimulation (session type ST+) resulted in significantly elevated response rates compared to the performance under the subthreshold current without visual stimuli (session type ST-). This effect was dose dependently blocked by competitive NMDA receptor antagonist (+/-)-CPP ((+/-)-3-(2-carboxypiperazin-4-yl)-propyl-1-phosphonic acid) and CGS 19755 (cis-4-(phosphonomethyl) piperidine-2-carboxylic acid). The present findings suggest that the activation of intracranial self-stimulation induced by a conditioned visual stimulus is dependent on the NMDA receptor functioning.