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Focal stimulation of specific pathways in the rat hippocampus causes a reduction in radioligand binding to the haloperidol-sensitive sigma receptor

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Summary

Focal electrical stimulation of selected excitatory pathways in the hippocampal slice caused a decrease in the binding of [3H]-1,3-di(2-tolyl)guanidine (DTG) or [3H]-(+)-3-[hydroxyphenyl]-N-(1-propyl)piperidine ((3H)-(+)3-PPP) to haloperidol-sensitive sigma binding sites in the slice. Activation of the mossy fibers or perforant path by high frequency electrical stimulation caused the reduction in [3H]-DTG binding; whereas activation of fibers in the strata radiatum, lacunosummoleculare, alveus, or oriens did not affect [3H]-DTG binding. The decrease in binding observed was calcium-dependent and tetrodotoxin sensitive and varied with the frequency, intensity, and duration of stimulation. Although haloperidol-sensitive [3H]-DTG binding sites are distributed throughout the hippocampus, stimulation of the perforant path or mossy fibers resulted in a significant reduction in binding only in the dentate region of the slice. The decrease in binding following perforant path stimulation was blocked by the glutamate receptor antagonist 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX); whereas the decrease in binding caused by mossy fiber stimulation was not affected by CNQX or DL-APV. The results obtained support the hypothesis that activation of the granule cells in the hippocampal slice caused the release of an endogenous ligand which acts at the haloperidol-sensitive sigma binding site in the dentate gyrus.

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Authors and Affiliations

  1. Department of Pharmacology SJ-30, University of Washington, 98195, Seattle, WA, USA

    M. A. Connor & C. Chavkin

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  1. M. A. Connor
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  2. C. Chavkin
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Connor, M.A., Chavkin, C. Focal stimulation of specific pathways in the rat hippocampus causes a reduction in radioligand binding to the haloperidol-sensitive sigma receptor. Exp Brain Res 85, 528–536 (1991). https://doi.org/10.1007/BF00231736

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  • DOI: https://doi.org/10.1007/BF00231736

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