Summary
As a stress model, a forced swimming test was applied to mice; and a typical behavioral change, an immobile posture, was recognized. This affected the brain monoamine levels significantly. The norepinephrine concentration was reduced, while that of its product was increased; and in the case of dopamine, both the amount of the amine and its product were increased. Stress increased the levels of serotonin and its product in the brain. The effects of RS-8359, (±)-4-(4-cyanophenyl)amino-6,7-dihydro-7-hydroxy-5H-cyclopenta[d]-pyrimidine, a new inhibitor of type A monoamine oxidase, on the behavioral and biochemical changes caused by forced swimming were also investigated. RS-8359 significantly improved the immobile posture elicited by the forced swimming test. It reduced the increased turnover of norepinephrine and serotonin systems caused by swimming. These results suggest that the effect of RS-8359 on behavioral and biochemical changes by stress may be mainly due to its effects on norepinephrine and serotonin systems, presumably by the inhibition of type A monoamine oxidase.
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References
Blanchard DC, Cholvanich P, Blanchard RJ, Clow DW, Hammer Jr RP, Rowlett JK, Bardo MT (1991) Serotonin, but not dopamine, metabolites are increased in selected brain regions of subordinate male in a colony environment. Brain Res 568: 61–66
Burkard WP, Bonetti EP, Da Prada M, Martin JR, Polc P, Schaffner R, Scherschlicht R, Hefti F, Müller RKM, Wyss P, Haefely W (1989) Pharmacological profile of moclobemide, a short-acting and reversible inhibitor of monoamine oxidase type A. J Pharmacol Exp Ther 248: 391–399
Carlsson A, Lindqvist M (1973) Effect of ethanol on the hydroxylation of tyrosine and tryptophan in rat brain in vivo. J Pharm Pharmacol 25: 437–440
Cicardo VH, Carbone SE, De Rondina DC, Mastronardi IO (1986) Stress by forced swimming in the rat: effects of mianserin and moclobemide on GABAergic-monoaminergic systems in the brain. Comp Biochem Physiol 83 C: 133–135
Dunn AJ (1988) Changes in plasma and brain tryptophan and brain serotonin and 5-hydroxyindoleacetic acid after footshock stress. Life Sci 42: 1847–1853
Freed CR, Yamamoto BK (1985) Regional brain dopamine metabolism: a marker for the speed, direction, and posture of moving animals. Science 229: 62–65
Iuvone PM, Dunn AJ (1986) Tyrosine hydroxylase activation in mesocortical 3,4-dihydroxyphenylethylamine neurons following footshock. J Neurochem 47: 837–844
Joseph MH, Kennett GA (1983) Stress-induced release of 5-HT in the hippocampus and its dependence on increased tryptophan availability: an in vivo electrochemical study. Brain Res 270: 251–257
Kumagae Y, Matsui Y, Iwata N (1990) Participation of type A monoamine oxidase in the activated deamination of brain monoamines shortly after reperfusion in rats. Jpn J Pharmacol 54: 407–413
Kumagae Y, Matsui Y, Iwata N (1991) Deamination of norepinephrine, dopamine, and serotonin by type A monoamine oxidase in discrete regions of the rat brain and inhibition by RS-8359. Jpn J Pharmacol 55: 121–128
Kvetnansky R, Sabban EL (1993) Stress-induced changes in tyrosine hydroxylase and other catecholamine biosynthetic enzymes. In: Naoi M, Parvez H (eds) Tyrosine hydroxylase; from discovery to cloning. VSP International Science Publishers, Zeist Netherlands, pp 258–287)
Lookingland KJ, Shannon NJ, Chapin DS, Moore KE (1986) Exogenous tryptophan increases synthesis, storage, and intraneuronal metabolism of 5-hydroxytryptamine in the rat hypothalamus. J Neurochem 47: 205–212
Matsui Y, Kumagae Y (1990) Monoamine oxidase inhibitors prevent striatal neuronal necrosis induced by transient forebrain ischemia. Neurosci Lett 126: 175–178
Oka K, Ashiba G, Kiss B, Nagatsu T (1982) Short-term effect of stress on tyrosine hydroxylase activity. Neurochem Int 4: 375–382
Porsolt RD, Le Pichon M, Jalfre M (1977 a) Depression: a new animal model sensitive to antidepressant treatments. Nature 266: 730–732
Porsolt RD, Bertin A, Jalfre M (1977b) Behavioural despair in mice: a primary screening test for antidepressants. Arch Int Pharmacodyn 229: 327–336
Porsolt RD, Bertin A, Blavet N, Deniel M, Jalfre M (1979) Immobility induced by forced swimming in rats: effects of agents which modify central catecholamine and serotonin activity. Eur J Pharmacol 57: 201–210
Shimizu N, Take S, Hori T, Oomura Y (1992) In vivo measurement of hypothalamic serotonin release by intracerebral microdialysis: significant enhancement by immobilization stress in rats. Brain Res Bull 28: 727–734
Willner P (1990) Animal models of depression: an overview. Pharmacol Ther 45: 425–455
Yamamoto BK, Freed CR (1982) The trained circling rat: a model for inducing unilateral caudate dopamine metabolism. Nature 298: 467–468
Yamamoto BK, Freed CR (1984) Asymmetric dopamine and serotonin metabolism in nigrostriatal and limbic structures of the trained circling rat. Brain Res 297: 115–119
Yamamoto BK, Lane RF, Freed CR (1982) Normal rats trained to circle show asymmetric caudate dopamine release. Life Sci 30: 2155–2162
Yokoyama T, Karube T, Iwata N (1989) Comparative studies of the effects of RS-8359 and safrazine on monoamine oxidase in-vitro and in-vivo in mouse brain. J Pharm Pharmacol 41: 32–36
Zacharko RM, Anisman H (1989) Pharmacological, biochemical, and behavioral analyses of depression: animal models. In: Koob GF, Ehlers CL, Kupfer DJ (eds) Animal models of depression. Birkhäuser, Boston, pp 205–211
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Miura, H., Naoi, M., Nakahara, D. et al. Changes in monoamine levels in mouse brain elicited by forced-swimming stress, and the protective effect of a new monoamine oxidase inhibitor, RS-8359. J. Neural Transmission 94, 175–187 (1993). https://doi.org/10.1007/BF01277023
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DOI: https://doi.org/10.1007/BF01277023