[Effects of OPC-24439, a sigma ligand, on neuronal activities in the hippocampus].
Sigma receptors in the central nervous system have been considered to play an important role in the modulation of mental diseases and memory/learning. However, the physiological function of sigma receptors still remains unknown. To elucidate physiological functions of the sigma receptors in modulation of neuronal activities, the effects of OPC-24439 (a sigma receptor ligand) on neuronal activities in hippocampal slices were studied with electrophysiological methods. Hippocampal slices (thickness ca. 450 microns) were prepared from male Wistar rats (4-7 weeks of age). In extracellular recording, population spikes in the CA1 region evoked by stimulation applied to the Schaffer collateral/commissural fibers were suppressed by OPC-24439 (1-100 microM) in a dose-dependent manner. This inhibition was antagonized by simultaneously applied haloperidol at 1 microM. In intracellular recording experiments, OPC-24439 (100 microM) did not affect the resting membrane potentials of neurons recorded. In addition, OPC-24439 had no effects on depolarization and firing induced by glutamate. These results indicate that sigma receptor activation caused suppression of neuronal activities in the hippocampus via the sigma receptors. This inhibition probably mediated via the suppression of ion channels that are not related to membrane potentials on post-synaptic neurons and/or sigma receptors on pre-synaptic neurons or interneurons.
Ishihara
K
K
Department of Pharmacology, Hiroshima University School of Medicine, Japan.
Akbar
M
M
Sasa
M
M
D000818:Animals; D001596:Benzylamines / Q000008:administration & dosage / Q000494:pharmacology*; D003521:Cyclopropanes / Q000008:administration & dosage / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004336:Drug Antagonism; D018698:Glutamic Acid / Q000494:pharmacology; D006220:Haloperidol / Q000494:pharmacology; D006624:Hippocampus / Q000187:drug effects*; D066298:In Vitro Techniques; D008024:Ligands; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D009474:Neurons / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D017480:Receptors, sigma / Q000187:drug effects*
D001596:Benzylamines; D003521:Cyclopropanes; D008024:Ligands; D017480:Receptors, sigma; C403863:m-(p-chlorobenzyloxy)-N-cyclopropylmethyl-N-methylbenzylamine; D018698:Glutamic Acid; D006220:Haloperidol