title: Dextromethorphan inhibits the glutamatergic synaptic transmission in the nucleus tractus solitarius of guinea pigs.
abstract: Dextromethorphan (DEX) is a widely used non-opioid antitussive. However, the precise site of action and its mechanism were not fully understood. We examined the effects of DEX on AMPA receptor-mediated glutamatergic transmission in the nucleus tractus solitarius (NTS) of guinea pigs. Excitatory postsynaptic currents (evoked EPSCs: eEPSCs) were evoked in the second-order neurons by electrical stimulation of the tractus solitarius. DEX reversibly decreased the eEPSC amplitude in a concentration-dependent manner. The DEX-induced inhibition of eEPSC was accompanied by an increased paired-pulse ratio. Miniature EPSCs (mEPSCs) were also recorded in the presence of Cd(2+) or tetrodotoxin. DEX decreased the frequency of mEPSCs without affecting their amplitude. Topically applied AMPA provoked an inward current in the neurons, which was unchanged during the perfusion of DEX. BD1047, a σ-1-receptor antagonist, did not block the inhibitory effect of DEX on the eEPSCs, but antagonized the inhibition of eEPSCs induced by SKF-10047, a σ-1 agonist. Haloperidol, a σ-1 and -2 receptor ligand, had no influence on the inhibitory action of DEX. These results suggest that DEX inhibits glutamate release from the presynaptic terminals projecting to the second-order NTS neurons, but this effect of DEX is not mediated by the activation of σ receptors.
authors.affiliation: Laboratory of Neuropharmacology, School of Pharmacy, Aichi Gakuin University, Chikusa, Nagoya 464-8650, Japan.
authors.forename: Yoshiaki
authors.initials: Y
authors.lastname: Ohi
authors.forename: Saori
authors.initials: S
authors.lastname: Tsunekawa
authors.forename: Akira
authors.initials: A
authors.lastname: Haji
mesh_terms: D000818:Animals; D000996:Antitussive Agents / Q000737:chemistry / Q000494:pharmacology*; D002121:Calcium Channel Blockers / Q000494:pharmacology; D003915:Dextromethorphan / Q000737:chemistry / Q000494:pharmacology*; D004558:Electric Stimulation; D018691:Excitatory Amino Acid Antagonists / Q000737:chemistry / Q000494:pharmacology*; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects; D006168:Guinea Pigs; D066298:In Vitro Techniques; D008024:Ligands; D008297:Male; D018715:Microscopy, Video; D009419:Nerve Tissue Proteins / Q000819:agonists / Q000037:antagonists & inhibitors / Q000378:metabolism; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism; D009994:Osmolar Concentration; D018408:Patch-Clamp Techniques; D018091:Receptors, AMPA / Q000037:antagonists & inhibitors; D017480:Receptors, sigma / Q000819:agonists / Q000037:antagonists & inhibitors / Q000378:metabolism; D026941:Sodium Channel Blockers / Q000494:pharmacology; D017552:Solitary Nucleus / Q000187:drug effects*; D009435:Synaptic Transmission / Q000187:drug effects*; D000097605:Sigma-1 Receptor
chemical_list: D000996:Antitussive Agents; D002121:Calcium Channel Blockers; D003915:Dextromethorphan; D018691:Excitatory Amino Acid Antagonists; D008024:Ligands; D009419:Nerve Tissue Proteins; D018091:Receptors, AMPA; D017480:Receptors, sigma; D026941:Sodium Channel Blockers; D000097605:Sigma-1 Receptor; C106107:sigma-2 receptor