PHENCYCLIDINE SELECTIVELY INHIBITS N-METHYL-D-ASPARTATE-INDUCED HIPPOCAMPAL [H-3] NOREPINEPHRINE RELEASE

  • 1 February 1987
    • journal article
    • research article
    • Vol. 240  (2) , 492-497
Abstract
We have reported previously that phencyclidine (PCP) antagonizes N-methyl-D-aspartate (NMDA)-induced release of dopmine and acetycholine from slices of rat striatum and nucleus accumbens. In the present experiments, we examined the effect of PCP on NMDA and kainic acid (KA)-induced release of [3H] norepinephrine (NE) from superfused rat hippocampal slices. NMDA and KA stimulated the efflux of NE withe EC50 values of 192 and 245 .mu.M, respectively. The presence of 1.2 mM MgCl2 in the buffer abolished NMDA-induced release but had little effect on KA-induced release. PCP inhibited the release of [3H]NE induced by 100 .mu.M NMDA with an IC50 of 46 nM, but had no effect on the release of NE stimulated by 300 .mu.M KA. 2-Aminophosphonovalerate antagonized NMDA-induced release producing a parallel shift to the right in the concentration-response curve. However, PCP shifted the concentration-response curve to the right in a nonparallel fashion. Drugs with PCP-like properties, such as dexoxadrol and cyclazocine, inhibited NMDA-induced release, whereas related drugs such as levoxadrol, ethylketocyclazocine and morphine, which are not PCP-like, had no effect. These data suggest that PCP is a potent, selective, noncompetive inhibitor of amino acid-induced [3H]NE release and that this action of PCP is mediated through the PCP/sigma receptor.