Modulation of striatal acetylcholine concentrations by NMDA and the competitive NMDA receptor-antagonist AP-5: an in...

The effects of local perfusion with the competitive NMDA receptor antagonist 2-amino-5-phosphonovalerate (AP-5) and the glutamate receptor agonist N-methyl-D-aspartate (NMDA) on release of extracellular acetylcholine (ACh) and choline (Ch) in the dorsolateral striatum were studied using in vivo microdialysis in freely moving rats. AP-5 caused a dose-dependent decrease in ACh release that was counteracted by the addition of NMDA. Perfusion with AP-5 also decreased Ch levels. Local perfusion with NMDA induced an elevation of ACh release in low (10(-5) M), but not high (10(-2) M and 10(-3) M) concentrations, that were associated with massive cellular death. These inhibitory effects of AP-5 and the stimulatory effect of NMDA in non-neurotoxic dosages on ACh release provide further evidence for a tonic stimulation of striatal cholinergic interneurons by glutamatergic neurons via NMDA receptors.