26 2002 pp. 39 48 Activation of serotonergic system by step exercise in humans Shinichi Sano    ,  Mariko Kaba      ,  Masahiro Sakamoto Ikuko Sato-Suzuki ,  Hideho Arita Received October 10, 2002 5HTとし27 4121342 121342 14 41 6911 Bailey 8 Fernstrom 11 Pannier対Meeusen 30 Faculty of Foreign Languages Bunkyougakuin University Faculty of Pharmaceutical Sciences Toho University 1 2 7,29,43 24 a 5HT 31 22 15 30 500ml 500ml 15c 15 15 15 5-HT
5HT 60 30 60 120 180 3 B HPLC 15
HR
AT window 511
A NOVA T -test Table  1
/
Table 1 1.06 005 4 296 203 1.36 0.09 Changes of stepping rate, respiration rate and stepping/respiration ratio Fig.1 during the exercise Table  2 Fig.2 5HT 0.01 30 005 30 60 0.05 F ig.3 Fig.4
15 30 5HT as 5HT 5HT 14,2022,41 Jacobs 5HT 14 5HT 41 5HT 197 5HT 1,28 Jacobs 1,20 5HT 5HT 5HT 5HT 2022 5HT 5HT 17 18 5HT 5HT 5HT 24 5HT 5HT 5HT 7 25 8 67 15 5HT BBB BBB 8,19,23,40 10:39 BBB 5HT 21,38 HT 35 5 5HT 1634 
 
 
 5 5HT 12 G.K. Aghajanian, C.P. Vandermaelen, Specific systems of the reticular core: serotonin. In: Mountcastle (Eds.), Handbook of Physiology, Vol. 4, Amer. Physiol. Soc., Maryland, 1984, pp.237-256. M.L. A tzenstein, J. Korf, On the elimination of centrally formed 5hydroxyindoleacetic acid by cerebrospinal fluid and urine, J. Neurochem. 32 (1979) 1227-1233. L.G. Almeida-Montes, V. Valles-Sanchez, J. Moreno-Aguilar, R.A. Chavez-Balderas, J.A. Carcia- Marin, J.F. C. Sotres, G.H. Relation of serum cholesterol, lipid, serotonin and tryptophan levels to severity of depression and to suicide attempts, J. Psychiatry Neurosci. 25 (2000) 371-377. S. Auerbach, C. Fornal, B.L. Jacobs, Response of serotonin-containing neurons in nucleus raphe magnus to morphine, noxious stimuli, and periaqueductal gray stimulation in freely moving cats, Exp. Neurol. 88 (1985) 609-628. D. Baldwin, S. Rudge, The role of serotonin in depression and anxiety, Int. Clin. Psychopharmacol. 9 (1995) 41-45. S.P. Bailey, J.M. Davis, E.N. A hlborn, Serotonergic agonists and antagonists affect endurance performance in the rat, Int. J. Sports Med. 14 (1993) 330333 E. Blomstrand, D. Perrett, M. Parry-Billings, E.A. Newsholme, Effect of sustained exercise on plasma amino acid concentrations and on 5 hydroxytryptamine metabolism in six different brain regions in the rat, A cta Physiol. Scand. 136 (1989) 473-481. S. Brõer, N. Brookes, Transfer of glutamine between astrocytes and neurons, J. Neurochem. 77 (2001) 705-719. F. Chaouloff, D. Laude, J.L.Elghozi, Physical exercise: evidence for differential consequences of tryptophan on 5-HT sysnthesis and metabolism in central serotonergic cell bodies and terminals, J. Neural Transm. 78 (1989) 121-130 R.H. Edwards, Drug delivery via the blood-brain barrier, Nat. Neurosci. 4 (2001) 221-222. 10 J.D. Fernstrom, Dietary amino acids and brain function. J Am Diet Assoc. 94 (1994) 71-77. 11 CA. Fornal, WJ. Litto, D.A. Morilak, B.L. Jacobs, Single-unit responses of serotonergic neurons to 12 glucose and insulin administration in behaving cats. A m. J. Physiol. 257 (1989) R1345R1353 C.A. Fornal, W.J. Litto, D.A. Morilak, B.L. Jacobs, Single-unit responses of serotonergic dorsal raphe 13 nucleus neurons to vascactive drug administration in freely moving cats, Am. J. Physiol. 259 (1990) R963R972 C.A. Fornal, C.W. Metzler, F. Marrosu, L.E. Ribiero-do-Valle, B.L. Jacobs, A subgroup of dorsal 14 raphe serotonergic neurons in the cat is strongly activated during oral-buccal movements, Brain Res. 716 (1996)123-133 M.J. Garvey, R. Noyes, Jr., C. Woodman, C. Laukes, The association of urinary 5- 15 hydroxyindoleacetic acid and vanillylmandelic acid in patients with generalized anxiety, Neuropsychobiology 31 (1995) 69 J.H. Greist, M.H. Klein, R.R. Eischens, J. Faris, A.S. Gurman, W.P. Morgan, Running as treatment for 16 depression. Compr. Psychiatry 20 (1979) 41-54 17 S. Grillner, P. Wallen, L. Brodin, A. Lansner, Neuronal network generating locomotor behavior in lamprey: circuitry, transmitters, membrane properties, and simulation, Annu. Rev. Neurosci. 14 (1991) 169-199 J.R. Holtman, Jr., N.C. Anastasi, W.P. Norman, K.L. Dretchen, Effect of electrical and chemical 18 stimulation of the raphe obscurus on phrenic nerve activity in the cat, Brain Res. 362 (1983) 214- 20 K. Hosoya, M. Sugawara, H. Asaba, T. Terasaki, Blood-blain barrier produces significant efflux of L- 19 aspartic acid but not D-aspartic acid: in vivo evidence using the brain efflux index method, J. Neurochem. 73 (1999) 1206-1211. B.L. Jacobs, Serotonin and behavior: emphasis on motor control, J. Clin. Psychiatry 52 (1991) 17-23 30 BL. Jacobs, E.C. Azmitia, Structure and function of the brain serotonin system, Physiol. Rev. 72 21 (1992) 165-229. B.L. Jacobs, C.A. Fornal, Activity of serotonergic neurons in behaving animals, 22 Neuropsychopharmacology 21 (1999) 95-155. A. Kakee, H. Takanaga, T, Terasaki, M. Naito, T. Tsuruo, Y. Sugiyama, Efflux of suppressive 23 neurotransmitter, GABA, across the blood-brain barrier, J. Neurochem. 79 (2001) I.P. Kema, E.G.E. de Vries, F.A.J.Muskiet, Clinical chemistry of serotonin and metabolites, J. 24 Chromatogr. 747 (2000) 33-48坂H.P.H. Kremer, J. G. Goekoop, G.M.J. Van Kempen, Clinical use of the determination of serotonin in whole blood, J. Clin. Psychopharmacol. 10 (1990) 8387. J.W. Maas, S.E. Hattox, N.M. Greene, D.H. Landis, Estimates of dopamine and serotonin sysnthesis 26 by the awake human brain, J. Neurochem. 34 (1980) 1547-1549. J.W. Maas, J.R. Leckman, Relationships between central nervous system noradrenergic function 27 and plasma and urinary MHPG and other norepinephrine metabolites, Maas, MHPG: Basic mechanisms and psychopathology (1983) p.33-43, Acad. Press, NY. 28 R.B. McCall, G.K. Aghajanian, Serotonergic facilitation of facial motoneuron excitation, Brain Res. 169 (1979) 11-27. R.G. McMurray, C.J. Hardy, et al, Neuroendocrine responses of type A individuals to exercise. & Behavioral Medicine. 15-2 (1989) 84-92 R.K. Meeusen, F. Thorre, S. Chaculoff, K. De Sarre, C. Meurleir, Edinger, and Y. Michotte, Effects 30 of tryptophan and / or acute running on extracellular 5HT and 5HIAA levels in the hippocampus of food deprived rats. Brain Res. 740 (1996) 245-252. 5 31 5HT 25 (2000) 237. HT 32 J.L. Pannier, J.J. Bouckert, R.A. Lefebvre, The antiserotonin agent pizotifen does noto increase endurance performance in humans, European Journal of Applied Physiology and Occupational Physiology. 721-2 (1995) 175-178 JS. Raglin, W.P. Morgan, Influence of exercise and quiet rest on state anxiety and blood pressure, 33 Med. Sci. Sports Exerc. 19 (1987) 456-463 C.P. Ransford, A role for amines in the antidepressant effect of exercise: a review, Me. Sci. Sports 34 Exerc. 14 (1982) 1-10 L.E. Ribeiro-do-Valle, C.W. Metzler, B.L. Jacobs, Facilitation of masseter EMG and masseteric fjaw- 35 closure) reflex by serotonin in behaving cats, Brain Res. 550 (1991) 197-204. M.J. Sarrias, P. Cabre, E. Martinez, F. Artigas, Relationship between serotoninergic measures in 36 blood and cerebrospinal fluid simultaneously obtained in humans. J Neurochem. 54 (1990) 783-786. S. Sano, M. Kaba, M. Sakamoto, I.S. Suzuki, H. A rita, A ctivation of serotonergic nervous system by 37 human rhythmical exercise (II) Neuroscience Research Supplement 25 (2001) S69 H.W.M. Steinbusch, Serotonin-immunoreactive neurons and their projections in the CNS. In: A. 38 Björklund, T. Hokfelt, M.J. Kuhar (Eds.), Handbook of Chemical Neuroanatomy, Vol. 3, Elsevier, Amsterdam, 1984, pp.68-125. I. Tamai, A. Tsuji, Transporter-mediated permeation of drugs across the blood-blain barrier, J. 39 Pharm Sci. 89 (2000) 1371-1388. T. Terasaki, K. Hosoya, The blood-brain barrier efflux transporters as a detoxifying system for the 40 brain, Adv. Drug Deliv. Rev. 36 (1989) 195-209. S.C. Veasey, C.A. Fornal, C.W. Metzler, B.L. Jacobs, Response of serotonergic caudal raphe neurons 41 in relation to specific motor activities in freely moving cats, J. Neurosci. 15 (1995) 5346-5359. L.O. Wilkinson, B.L. Jacobs, Lack of response of serotonergic neurons in the dorsal raphe nucleus of 42 freely moving cats to stressful stimuli, Exp. Neurol. 101 (1988) 445457. Wilson, W.M., and R.J. Maughan: Evidence for a possible role of 5-hydroxytryptamine in the 43 genesis of fatigue in man : administration of paroxetine. a 5HT re-uptake inhibitor, reduces the capacity to perform prolonged exercise. Exp. Physiol. 77 (1992) 921-924.