Summary
The acute and chronic effects of capsaicin (s.c.) on the monoamines in the preoptic region + hypothalamus (RPO-H), spinal cord, substantia nigra and striatum were studied. Levels of DOPA, DA, DOPAC, HVA, 3-MT, NA, Trp, 5-HTP, 5-HT and 5-HIAA were determined by means of liquid chromatography (HPLC-EC). In response to acute capsaicin treatment, the levels of DA, DOPAC and DA synthesis rate (DOPA formation) were increased in a dose-dependent manner in the RPO-H and spinal cord. The disappearance rate of NA was accelerated in both regions. In substantia nigra, increased DOPAC levels were found whereas the levels of 3-MT were decreased in striatum after acute capsaicin treatment. Only minor changes on the levels of 5-HT and 5-HIAA in the regions studied were noted. Neonatal or adult capsaicin treatment failed to affect the levels of NA, DA and 5-HT (measured two months or five weeks after injection, respectively) in the regions studied. A capsaicin injection to rats pretreated with the drug as adults did not affect either the monoamines in the RPO-H and spinal cord or the body temperature. In contrast, in rats pretreated with capsaicin as neonates, a second injection of the drug to adult animals elicited hypothermia and changes in monoamines similar to those observed in naive animals.
Article PDF
Similar content being viewed by others
Avoid common mistakes on your manuscript.
References
Bligh J (1979) The central neurology of mammalian thermoregulation. Neuroscience 4: 1213–1236
Brück K, Hinckel P (1982) Thermoafferent systems and their adaptive modifications. Pharmacol Ther 17: 357–381
Cantor A, Satinoff E (1976) Thermoregulatory responses to intraventricular norepinephrine in normal and hypothalamic-damaged rats. Brain Res 108: 125–141
Garlsson A, Lindqvist M (1973) Effect of ethanol on the hydroxylation of tyrosine and tryptophan in rat brainin vivo. J Pharm Pharmacol 25: 437–440
Commissiong JW, Neff NH (1979) Current status of dopamine in the mammalian spinal cord. Biochem Pharmacol 28: 1569–1573
Corrodi H, Fuxe K, Hökfelt T (1967) A possible role played by central monoamine neurones in thermo-regulation. Acta Physiol Scand 71: 224–232
Cox B, Kerwin RW, Lee TF, Pycock CJ (1980) A dopamine-5-hydroxytryptamine link in the hypothalamic pathways which mediate heat loss in the rat. J Physiol (Lond) 303: 9–21
Dawbarn D, Harmar AJ, Pycock CJ (1981) Intranigral injection of capsaicin enhances motor activity and depletes nigral 5-hydroxytryptamine but not substance P. Neuropharmacology 20: 341–346
Dib B (1982) Effects of intracerebroventricular capsaicin on thermoregulatory behavior in the rat. Pharmacol Biochem Behav 16: 23–27
Dib B (1983) Dissociation between peripheral and central heat loss mechanisms induced by neonatal capsaicin. Behav Neurosci 97: 822–829
Felice LJ, Felice JD, Kissinger PT (1978) Determination of catecholamines in rat brain parts by reverse-phase ion-pair liquid chromatography. J Neurochem 31: 1461–1465
Gamse R, Leeman SE, Holzer P, Lembeck F (1981) Differential effects of capsaicin on the content of somatostatin, substance P and neurotensin in the nervous system of the rat. Naunyn-Schmiedebergs Arch Pharmacol 317: 140–148
Hajos M, Obal FJr, Jancso G, Obal F (1983) The capsaicin sensitivity of the preoptic region is preserved in adult rats pretreated as neonates, but lost in rats pretreated as adults. Naunyn-Schmiedebergs Arch Pharmacol 324: 219–222
Hajos M, Obal FJr, Jancso G, Obal F (1985) Capsaicin impairs preoptic serotonin-sensitive structures mediating hypothermia in rats. Neurosci Lett 54: 97–102
Holzer P, Saria A, Skofitsch G, Lembeck F (1981) Increase in tissue concentrations of histamine and 5-hydroxytryptamine following capsaicin treatment of newborn rats. Life Sci 29: 1099–1105
Hori T (1981) Thermosensitivity of preoptic and anterior hypothalamic neurons in the capsaicin-desensitized rat. Pfiügers Arch 389: 297–299
Hori T, Tsuzuki S (1981) Thermoregulation in adult rats which have been treated with capsaicin as neonates. Pflügers Arch 390: 219–223
Hori T (1984) Capsaicin and central control of thermoregulation. Pharmac Ther 26: 389–416
Jancso G, Hökfelt T, Lundberg JM, Kiraly E, Halasz N, Nilson G, Terenius L, Rehfeld J, Steinbuch H, Verhofstadt A, Elde R, Said S, Brown M (1981) Immunohistochemical studies on the effects of capsaicin on the spinal and medullary peptide and monoamine neurons using antisera to substance P, gastrin/CCK, somatostatin, VIP, enkephalin, neurotensin and 5-hydroxytryptamine. J Neurocytol 10: 963–980
Jancso G, Jancso-Gabor A (1980) Effects of capsaicin on morphine analgesia-possible involvement of hypothalamic structures. Naunyn-Schmiedebergs Arch Pharmacol 311: 285–288
Jancso G, Kiraly E (1980) Distribution of chemosensitive primary sensory afferents in the central nervous system of the rat. J Comp Neurol 190: 781–792
Jancso G, Kiraly E, Jancso-Gabor A (1980) Chemosensitive pain fibres and inflammation. Int J Tiss Reac 2: 57–66
Jancso G, Wollemann M (1977) The effect of capsaicin on the adenylate cyclase activity of the brain. Brain Res 123: 323–329
Jancso-Gabor A (1976) Characteristics of the long-lasting “chemical analgesia” induced by capsaicin. In: Knoll J, Vizi ES (eds) Symposium on analgesics. Akademia Kiado, Budapest, pp 161–166
Jancso-Gabor A, Szolcsanyi J, Jancso N (1970 a) Irreversible impairment of thermoregulation induced by capsaicin and similar pungent substances in rats and guinea-pigs. J Physiol (Lond) 206: 495–507
Jancso-Gabor A, Szolcsanyi J, Jancso N (1970 b) Stimulation and desensitization of the hypothalamic heat-sensitive structures by capsaicin in rats. J Physiol (Lond) 208: 449–459
Jancso N (1968) Desensitization with capsaicin and related acylamides as a tool for studying the function of pain receptors. In: Lim RKS (ed) Pharmacology of pain. Pergamon Press, Oxford, pp 33–55
Jancso N, Jancso-Gabor A, Szolcsanyi J (1967) Direct evidence for neurogenic inflammation and its prevention by denervation and pretreatment with capsaicin. Br J Pharmacol Chemother 31: 138–151
Jensen TS, Yaksh TL (1984) Effects of intrathecal dopamine agonist, apomorphine, on thermal and chemical evoked noxious responses in rats. Brain Res 296: 285–293
Kehr W, Carlsson A, Lindqvist M, Magnusson T, Atack C (1972) Evidence for a receptor-mediated feedback control of striatal tyrosine hydroxylase activity. J Pharm Pharmacol 24: 744–747
Lin MT, Chandra A, Tsay BL, Chern YF (1982) Hypothalamic and striatal dopamine receptors activation inhibits heat production in the rat. Am J Physiol 242: R471-R481
Lowry OH, Rosebrough NJ, Farr AL, Randell RJ (1951) Protein measurement with the folin phenol reagent. J Biol Chem 193: 265–275
Lundberg JM, Franco-Cereceda A, Hua X, Hökfelt T, Fischer JA (1985) Coexistence of substance P and calcitonin gene-related peptide-like immunoreactivities in sensory nerves in relation to cardiovascular and bronchoconstrictor effects of capsaicin. Eur J Pharmacol 108: 315–319
Magnusson O, Nilsson LB, Westerlund D (1980) Simultaneous determination of dopamine, dopac and homovanillic acid. Direct injection of supernatants from brain tissue homogenates in a liquid chromatography-electrochemical detection system. J Chromatogr 221: 237–247
Markwell MAK, Haas SM, Bieber LL, Tolbert NE (1978) A modification of the Lowry-procedure to simplify protein determination in membrane and lipoprotein samples. Analyt Biochem 87: 206–210
Monsenereenusorn Y, Kongsamut S, Pezalla PD (1982) Capsaicin: a literature survey. CRC Crit Rev Toxicol 10: 321–339
Mueller GP (1981) Beta-endorphin immunoreactivity in rat plasma: variations in response to different physical stimuli. Life Sci. 29: 1669–1674
Nagy JI (1982) Capsaicin: a chemical probe for sensory neuron mechanisms. In: Iversen LL, Iversen SD, Snyder SH (eds) Handbook of psychopharmacology, vol 15. Plenum Press, New York, pp 185–235
Nagy JI, Vincet SR, Staines WA, Fibiger HC, Reisine TD, Yamamura HI (1980) Neurotoxic action of capsaicin on spinal substance P neurons. Brain Res 186: 435–444
Obal FJr, Benedek G, Jancso-Gabor A, Obal F (1979) Salivary cooling, escape reaction and heat pain in capsaicin-desensitized rats. Pflügers Arch 382: 249–254
Obal FJr, Benedek G, Jancso-Gabor A, Obal F (1980) Tail skin vasodilatation and bath test in capsaicin-desensitized rats. Pflügers Arch 387: 183–188
Obal FJr, Hajos M, Benedek G, Obal F, Jancso-Gabor A (1981) Impaired heat discrimination learning after capsaicin treatment. Physiol Behav 27: 977–981
Obal FJr, Jancso G, Jancso-Gabor A, Obal F (1983) Vasodilatation on preoptic heating in capsaicin-treated rats. Experientia 39: 221–223
Reddy SVR, Maderdrut JL, Yaksh TL (1980) Spinal cord pharmacology of adrenergic agonist-mediated antinociception. J Pharmacol Exp Ther 213: 525–533
Reid WD, Volicer L, Smookler M, Beaven MA, Brodie BB (1968) Brain amines and temperature regulation. Pharmacologist 1: 329–344
Saria A, Skofitsch G, Lembeck F (1982) Distribution of capsaicin in rat tissues after systemic administration. J Pharm Pharmacol 34: 273–275
Sheard MH, Aghajanian GK (1967) Neural release of brain serotonin and body temperature. Nature 216: 495–496
Shum A, Sole MJ, van Loon GR (1982) Simultaneous measurement of 5-hydroxytryptophan and 1-dihydroxyphenylalanine by high-performance liquid chromatography with electrochemical detection. Measurement of serotonin and catecholamine turnover in discrete brain regions. J Chromatogr 228: 123–130
Simmonds MA (1971) Inhibition by atropin of the increased turnover of noradrenaline in the hypothalamus of rats exposed to cold. Br J Pharmac 41: 224–229
Simmonds MA, Iversen LL (1969) Thermoregulation: Effects of environmental temperature on turnover of hypothalamic norepinephrine. Science 163: 473–474
Singer EA, Sperk G, Schmid R (1982) Capsaicin does not change tissue levels of glutamic acid, its uptake, or release in the rat spinal cord. J Neurochem 38: 1383–1386
Szikszay M, Obal FJr, Obal F (1982) Dose-response relationships in the thermoregulatory effects of capsaicin. Naunyn-Schmiedebergs Arch Pharmacol 320: 97–100
Szolcsanyi J (1982) Capsaicin type pungent agents producing pyrexia. In: Milton AS (ed) Handbook of experimental pharmacology, vol 60. Springer, Berlin Heidelberg New York, pp 437–478
Szolcsanyi J, Joo F, Jancso-Gabor A (1971) Mitochondrial changes in preoptic neurons after capsaicin desensitization of the hypothalamic thermodetectors in rats. Nature 229: 116–117
Virus RM, McManus DQ, Gebhart GF (1983) Capsaicin treatment in adult Wistar-Kyoto and spontaneously hypertensive rats: neurochemical effects in the spinal cord. European J Pharmacol 92: 1–8
Weiss BL, Aghajanian GK (1971) Activation of brain serotonin metabolism by heat: role of midbrain raphe neurons. Brain Res 26: 37–48
Weiss JM, Goodman PA, Lositio BG, Corrigan S, Charry JM, Bailey WH (1981) Behavioral depression produced by an uncontrollable stressor: Relationship to norepinephrine, dopamine and serotonin levels in various regions of rat brain. Brain Res Rev 3: 167–205
Yamawaki S, Lai H, Horita A (1983) Dopaminergic and serotonergic mechanisms of thermoregulation: mediation of thermal effects of apomorphine and dopamine. J Pharmacol Exp Ther 227: 383–388
Yaksh TL, Wilson PR (1979) Spinal serotonin terminal system mediates antinociception. J Pharmacol Exp Ther 209: 446–453
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Hajós, M., Svensson, K., Nissbrandt, H. et al. Effects of capsaicin on central monoaminergic mechanisms in the rat. J. Neural Transmission 66, 221–242 (1986). https://doi.org/10.1007/BF01260916
Received:
Revised:
Issue Date:
DOI: https://doi.org/10.1007/BF01260916