title: Serotonergic fibers induce a long-lasting inhibition of monosynaptic reflex in the neonatal rat spinal cord.
abstract: The transmitter mechanism of a long-lasting descending inhibition of the monosynaptic reflex was investigated in the isolated spinal cord of the neonatal rat. The monosynaptic reflex elicited by dorsal root stimulation was recorded extracellularly from a lumbar ventral root (L3-L5). Electrical stimulation of the upper thoracic part of the hemisected cord caused an inhibition lasting about 40 s of the monosynaptic reflex. This descending inhibition was markedly attenuated by perfusing the spinal cord with reserpine (1 microM) or 5,7-dihydroxytryptamine (10 microM) for 2-6 h. The perfusion with reserpine (1 microM) for 4 h significantly decreased the contents of 5-hydroxytryptamine, dopamine, and norepinephrine of the neonatal rat spinal cord, whereas the perfusion with 5,7-dihydroxytryptamine (10 microM) for 4 h decreased the contents of 5-hydroxytryptamine and dopamine. The descending inhibition was markedly potentiated by a 5-hydroxytryptamine uptake blocker, citalopram (10 nM), and was blocked by a 5-hydroxytryptamine antagonist, ketanserin (10-100 nM). Application of 5-hydroxytryptamine to the spinal cord induced an inhibition of the monosynaptic reflex, a later part of which was blocked by ketanserin. Ketanserin also moderately blocked inhibitions of the monosynaptic reflex caused by norepinephrine and dopamine. Phentolamine (10 microM) abolished the depressant actions of norepinephrine and dopamine, but did not affect that of 5-hydroxytryptamine or the descending inhibition. These results strongly suggest the involvement of 5-hydroxytryptamine, but not dopamine nor norepinephrine, in the descending inhibition. Besides ketanserin, the descending inhibition was blocked by ritanserin, haloperidol, and pipamperone, which have affinities to 5-hydroxytryptamine2 receptors, and also by spiperone and methiothepin, which are antagonists at both 5-hydroxytryptamine1 and 5-hydroxytryptamine2 receptors (all 1 microM). On the other hand, a 5-hydroxytryptamine1C and 5-hydroxytryptamine2 antagonist, mesulergine (1 microM), and 5-hydroxytryptamine3 antagonists, ICS 205-930 and quipazine (both 1 microM), did not depress either the descending inhibition or the 5-hydroxytryptamine-evoked inhibition of the monosynaptic reflex. The results with these antagonists favor the involvement of 5-hydroxytryptamine2 receptors although the results with mesulergine disagree with this notion. 5-Hydroxytryptamine1 agonists, such as 8-hydroxy-2-(di-n-propylamino)tetralin, buspirone, and 5-carboxyamidotryptamine, and a 5-hydroxytryptamine3 agonist, 2-methyl-5-hydroxytryptamine, induced a long-lasting inhibition of the monosynaptic reflex, which was blocked by ketanserin whereas a 5-hydroxytryptamine2 agonist, S-(+)-alpha-methyl-5-hydroxytryptamine, evoked a biphasic inhibition, in which only the later component was blocked by ketanserin.(ABSTRACT TRUNCATED AT 400 WORDS)
authors.affiliation: Department of Pharmacology, Faculty of Medicine, Tokyo Medical and Dental University, Japan.
authors.forename: H S
authors.initials: HS
authors.lastname: Yomono
authors.forename: H
authors.initials: H
authors.lastname: Suzuki
authors.forename: K
authors.initials: K
authors.lastname: Yoshioka
mesh_terms: D015116:5,7-Dihydroxytryptamine / Q000494:pharmacology; D000818:Animals; D000831:Animals, Newborn / Q000502:physiology*; D001679:Biogenic Amines / Q000378:metabolism; D015283:Citalopram / Q000494:pharmacology; D004594:Electrophysiology; D005260:Female; D066298:In Vitro Techniques; D007650:Ketanserin / Q000494:pharmacology; D008297:Male; D009412:Nerve Fibers / Q000502:physiology*; D010646:Phentolamine / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D012023:Reflex, Monosynaptic / Q000502:physiology*; D012110:Reserpine / Q000494:pharmacology; D012701:Serotonin / Q000502:physiology*; D013116:Spinal Cord / Q000166:cytology / Q000502:physiology*
chemical_list: D001679:Biogenic Amines; D015283:Citalopram; D015116:5,7-Dihydroxytryptamine; D012701:Serotonin; D012110:Reserpine; D007650:Ketanserin; D010646:Phentolamine