Focal stimulation of specific pathways in the rat hippocampus causes a reduction in radioligand binding to the haloperidol-sensitive sigma receptor.
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, lacunosum-moleculare, 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.
Department of Pharmacology SJ-30, University of Washington, Seattle 98195.
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D018750:6-Cyano-7-nitroquinoxaline-2,3-dione; D000818:Animals; D002118:Calcium / Q000502:physiology; D004558:Electric Stimulation; D006146:Guanidines / Q000378:metabolism; D006220:Haloperidol / Q000494:pharmacology*; D006624:Hippocampus / Q000502:physiology*; D008297:Male; D010880:Piperidines / Q000378:metabolism; D011810:Quinoxalines / Q000494:pharmacology; D011869:Radioligand Assay; D051381:Rats; D011919:Rats, Inbred Strains; D011957:Receptors, Opioid / Q000032:analysis* / Q000187:drug effects; D017480:Receptors, sigma
D006146:Guanidines; D010880:Piperidines; D011810:Quinoxalines; D011957:Receptors, Opioid; D017480:Receptors, sigma; D018750:6-Cyano-7-nitroquinoxaline-2,3-dione; C026539:preclamol; D006220:Haloperidol; C050232:1,3-ditolylguanidine; D002118:Calcium