Antagonism of N-methyl-D-aspartate (NMDA) evoked increases in cerebellar cGMP and striatal ACh release by phencyclidine (PCP) receptor agonists; evidence for possible allosteric coupling of NMDA and PCP receptors

Abstract

A comparison was made of the actions of phencyclidine receptor agonists and N-methyl-D-aspartate (NMDA) receptor antagonists in two well-defined neurochemical test systems. These included (i) [3H]acetylcholine release from striatal cholinergic interneurons in vitro, a system known to be positively modulated by corticostriatal excitatory amino acid inputs in vivo; and (ii) cerebellar cGMP level in vivo, an indicator of cerebellar Purkinje cell activity, which is also modulated by excitatory amino acid inputs. Using these neuronal systems, we report that phencyclidine receptor agonists demonstrated a noncompetitive antagonism of NMDA receptor agonist actions.