Failure of σ-receptor ligands to reduce the excitatory actions of N-methyl-DL-aspartate on rat spinal neurons in-vivo

Abstract

— Haloperidol and (+)‐3‐PPP, compounds with known affinity for the σ‐receptor, have been examined for their ability to reduce the excitatory actions of N‐methyl‐DL‐aspartate (NMDLA), quisqualate and kainate on rat spinal neurons in‐vivo. The actions of (‐)‐3‐PPP were also tested. Haloperidol was injected intravenously whereas the 3‐PPP enantiomers were administered by microelectrophoresis. Haloperidol had little effect on excitations evoked by NMDLA, quisqualate or kainate whereas both (+)‐ and (‐)‐3‐PPP usually enhanced, non‐selectively, responses to all three excitatory amino acid analogues. The results support suggestions that phencyclidine (PCP)‐like compounds with affinity for both PCP and σ‐receptors reduce neuronal excitations mediated by the N‐methyl‐D‐aspartate (NMDA) receptor via a selective effect at the PCP site.