NMDA-coupled and uncoupled forms of the PCP receptor: preliminary in vivo evidence for PCP receptor subtypes.

1. As reported for many other PCP receptor actions, the pharmacological profile of PCP receptor agonists and NMDA receptor antagonists were similar with regard to their effects on cerebellar cGMP levels in vivo. 2. PCP receptor agonists act to increase mesocortical dopamine (DA) metabolism and release. 3. This receptor action is stereospecific and is both dose- and time-dependent. 4. The actions of PCP on DA metabolism appear to involve PCP receptors both in the ventral tegmental area (VTA) and the cortical nerve terminal regions. 5. In contrast to many other systems which have been studied, competitive NMDA antagonists do not act in a manner similar to PCP agonists, with regard to mesocortical DA metabolism. 6. Sigma receptor ligands and NMDA agonists also do not alter mesocortical DA metabolism. 7. These data suggest that the PCP receptor population which modulates mesocortical dopaminergic neurons is not coupled to NMDA receptors.