The effects of sigma ligands on the release of glutamate from rat striatal slices

This study investigated the effects of sigma receptor ligands on the release of endogenous amino acid neurotransmitters from rat striatal slices. The effect of haloperidol on release in slices prepared from 6-hydroxydopamine lesioned animals was also tested. Haloperidol, the (+/-) reduced metabolite of haloperidol, rimcazole and ifenprodil specifically reduced potassium-stimulated release of glutamate with IC50 values between 20-60 microM. The release of aspartate, gamma-aminobutyric acid (GABA) and glycine was not affected. Haloperidol also reduced glutamate release from slices prepared from lesioned animals. The neuroleptic drug alpha-flupenthixol and the putative sigma receptor ligand R(+)3-(3-hydroxyphenyl)-N-(n-propyl) piperidine (3-PPP) had no effect on release. These effects of the sigma ligands show that the inhibition of glutamate release is specific to this amino acid and also that it is not due to dopamine receptor blockade as those ligands which have low affinity for dopamine receptors were also effective in reducing release. A presynaptic location for sigma receptor sites, possibly associated with ion channels, could account for the effects of these ligands on transmitter release.