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. 1982;333:511–529. doi: 10.1113/jphysiol.1982.sp014466

The thermoregulatory effects of noradrenaline, serotonin and carbachol injected into the rat spinal subarachnoid space

Richard M Lopachin 1, T A Rudy 1
PMCID: PMC1197261  PMID: 6897819

Abstract

1. We have examined the effects on thermoregulation in the rat of noradrenaline bitartrate (NA), 5-hydroxytryptamine hydrochloride (5-HT) and carbamylcholine chloride (CCh) injected into the lumbar spinal subarachnoid space via a chronic indwelling catheter.

2. Intrathecal injections of the monoamines and CCh reproducibly affected thermoregulation, whereas injections of control solutions had no effect.

3. Intrathecal injections of NA (0·01-0·30 μmol) produced a dose-dependent hypothermia associated with a decrease in tail skin vasomotor tone. Shivering activity was not depressed during the hypothermia and sometimes increased. Intrathecal administration of the α-adrenergic agonist clonidine (0·0175-0·070 μmol) elicited changes in Tc and Tsk similar to those induced by intrathecal NA.

4. Intrathecal 5-HT (0·030-0·90 μmol) elicited a dose-dependent hyperthermia accompanied by increased tail skin vasomotor tone and increased shivering.

5. CCh injected intrathecally (0·001-0·06 μmol) evoked a dose-dependent hyperthermia. During the period when core temperature was rising, tail skin vasomotor tone increased and shivering-like activity was present. Once the maximum core temperature had been reached, tail skin vasodilatation occurred. Vasodilatation persisted until core temperature had returned to normal.

6. Intravenous injections of 5-HT (0·30 and 0·90 μmol) or CCh (0·006 and 0·03 μmol) caused no thermoregulatory effect. The effects of these agents injected intrathecally were therefore not due to an action in the periphery.

7. Intravenous infusions of NA (0·06 and 0·10 μmol) produced hypothermia and transient tail skin vasodilatation. We suggest that an action at peripheral sites may have contributed to the effects produced by intrathecal injection of this monamine.

8. These findings suggest that spinal noradrenergic, serotonergic and cholinergic synapses may be importantly involved in the control of body temperature in the rat. The possible functional roles of these synapses and the putative spinal sites of action of the injected substances are discussed.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Ackerman D., Rudy T. A. Thermoregulatory characteristics of neurogenic hyperthermia in the rat. J Physiol. 1980 Oct;307:59–70. doi: 10.1113/jphysiol.1980.sp013423. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Alexander R. W., Davis J. N., Lefkowitz R. J. Direct identification and characterisation of beta-adrenergic receptors in rat brain. Nature. 1975 Dec 4;258(5534):437–440. doi: 10.1038/258437a0. [DOI] [PubMed] [Google Scholar]
  3. Beckman A. L. Effect of intrahypothalamic norepinephrine on thermoregulatory responses in the rat. Am J Physiol. 1970 Jun;218(6):1596–1604. doi: 10.1152/ajplegacy.1970.218.6.1596. [DOI] [PubMed] [Google Scholar]
  4. Bruinvels J. Effect of noradrenaline, dopamine and 5-hydroxytryptamine on body temperature in the rat after intracisternal administration. Neuropharmacology. 1970 May;9(3):277–282. doi: 10.1016/0028-3908(70)90077-8. [DOI] [PubMed] [Google Scholar]
  5. Buccafusco J. J., Brezenoff H. E. Mechanisms involved in the cardiovascular response to intracerebroventricular injection of noradrenaline and phentolamine. Neuropharmacology. 1977 Nov;16(11):775–780. doi: 10.1016/0028-3908(77)90136-8. [DOI] [PubMed] [Google Scholar]
  6. CARLSSON A., FALCK B., FUXE K., HILLARP N. A. CELLULAR LOCALIZATION OF MONOAMINES IN THE SPINAL CORD. Acta Physiol Scand. 1964 Jan-Feb;60:112–119. doi: 10.1111/j.1748-1716.1964.tb02874.x. [DOI] [PubMed] [Google Scholar]
  7. Christensen B. N., Perl E. R. Spinal neurons specifically excited by noxious or thermal stimuli: marginal zone of the dorsal horn. J Neurophysiol. 1970 Mar;33(2):293–307. doi: 10.1152/jn.1970.33.2.293. [DOI] [PubMed] [Google Scholar]
  8. Clark W. G., Clark Y. L. Changes in body temperature after administration of acetylcholine, histamine, morphine, prostaglandins and related agents. Neurosci Biobehav Rev. 1980 Summer;4(2):175–240. doi: 10.1016/0149-7634(80)90015-9. [DOI] [PubMed] [Google Scholar]
  9. Clark W. G., Clark Y. L. Changes in body temperature after administration of adrenergic and serotonergic agents and related drugs including antidepressants. Neurosci Biobehav Rev. 1980 Fall;4(3):281–375. doi: 10.1016/0149-7634(80)90002-0. [DOI] [PubMed] [Google Scholar]
  10. Coote J. H., Macleod V. H. The effect of intraspinal microinjections of 6-hydroxydopamine on the inhibitory influence exerted on spinal sympathetic activity by the baroreceptors. Pflugers Arch. 1977 Nov 23;371(3):271–277. doi: 10.1007/BF00586268. [DOI] [PubMed] [Google Scholar]
  11. Coote J. H., Macleod V. H. The influence of bulbospinal monoaminergic pathways on sympathetic nerve activity. J Physiol. 1974 Sep;241(2):453–475. doi: 10.1113/jphysiol.1974.sp010666. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. De Groat W. C., Ryall R. W. An excitatory action 0f 5-hydroxytryptamine on sympathetic preganglionic neurones. Exp Brain Res. 1967;3(4):299–305. doi: 10.1007/BF00237556. [DOI] [PubMed] [Google Scholar]
  13. Dhawan B. N., Johri M. B., Singh G. B., Srimal R. C., Viswesaram D. Effect of clonidine on the excitability of vasomotor loci in the cat. Br J Pharmacol. 1975 May;54(1):17–21. doi: 10.1111/j.1476-5381.1975.tb07404.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Glazer E. J., Ross L. L. Localization of noradrenergic terminals in sympathetic preganglionic nuclei of the rat: demonstration by immunocytochemical localization of dopamine-beta-hydroxylase. Brain Res. 1980 Mar 3;185(1):39–49. doi: 10.1016/0006-8993(80)90668-x. [DOI] [PubMed] [Google Scholar]
  15. Headley P. M., Duggan A. W., Griersmith B. T. Selective reduction by noradrenaline and 5-hydroxytryptamine of nociceptive responses of cat dorsal horn neurones. Brain Res. 1978 Apr 21;145(1):185–189. doi: 10.1016/0006-8993(78)90809-0. [DOI] [PubMed] [Google Scholar]
  16. Hellon R. F., Misra N. K. Neurones in the dorsal horn of the rat responding to scrotal skin temperature changes. J Physiol. 1973 Jul;232(2):375–388. doi: 10.1113/jphysiol.1973.sp010275. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Hellon R. F. Monoamines, pyrogens and cations: their actions on central control of bodytemperature. Pharmacol Rev. 1974 Dec;26(4):289–321. [PubMed] [Google Scholar]
  18. Hilton S. M., Spyer K. M. Central nervous regulation of vascular resistance. Annu Rev Physiol. 1980;42:399–441. doi: 10.1146/annurev.ph.42.030180.002151. [DOI] [PubMed] [Google Scholar]
  19. Jordan L. M., Kenshalo D. R., Jr, Martin R. F., Haber L. H., Willis W. D. Depression of primate spinothalamic tract neurons by iontophoretic application of 5-hydroxytryptamine. Pain. 1978 Aug;5(2):135–142. doi: 10.1016/0304-3959(78)90035-0. [DOI] [PubMed] [Google Scholar]
  20. Kayaalp S. O., Neff N. H. Regional distribution of cholinergic muscarinic receptors in spinal cord. Brain Res. 1980 Sep 8;196(2):429–436. doi: 10.1016/0006-8993(80)90406-0. [DOI] [PubMed] [Google Scholar]
  21. Kent D. L., Sladek J. R., Jr Histochemical, pharmacological and microspectrofluorometric analysis of new sites of serotonin localization in the rat hypothalamus. J Comp Neurol. 1978 Jul 15;180(2):221–236. doi: 10.1002/cne.901800203. [DOI] [PubMed] [Google Scholar]
  22. Lin M. T., Chai C. Y. Independence of spinal cord and medulla oblongata on thermal activity. Am J Physiol. 1974 May;226(5):1066–1072. doi: 10.1152/ajplegacy.1974.226.5.1066. [DOI] [PubMed] [Google Scholar]
  23. Lipton J. M. Thermosensitivity of medulla oblongata in control of body temperature. Am J Physiol. 1973 Apr;224(4):890–897. doi: 10.1152/ajplegacy.1973.224.4.890. [DOI] [PubMed] [Google Scholar]
  24. LoPachin R. M., Rudy T. A., Yaksh T. L. An improved method for chronic catheterization of the rat spinal subarachnoid space. Physiol Behav. 1981 Sep;27(3):559–561. doi: 10.1016/0031-9384(81)90350-4. [DOI] [PubMed] [Google Scholar]
  25. Loewy A. D., McKellar S. Serotonergic projections from the ventral medulla to the intermediolateral cell column in the rat. Brain Res. 1981 Apr 27;211(1):146–152. doi: 10.1016/0006-8993(81)90074-3. [DOI] [PubMed] [Google Scholar]
  26. Myslinski N. R., Randić M. Responses of identified spinal neurones to acetylcholine applied by micro-electrophoresis. J Physiol. 1977 Jul;269(1):195–219. doi: 10.1113/jphysiol.1977.sp011899. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Nelson D. L., Herbet A., Adrien J., Bockaert J., Hamon M. Serotonin-sensitive adenylate cyclase and [3H]serotonin binding sites in the CNS of the rat--II. Respective regional and subcellular distributions and ontogenetic developments. Biochem Pharmacol. 1980 Sep 15;29(18):2455–2463. doi: 10.1016/0006-2952(80)90349-4. [DOI] [PubMed] [Google Scholar]
  28. Neumayr R. J., Hare B. D., Franz D. N. Evidence for bulbospinal control of sympathetic preganglionic neurons by monoaminergic pathways. Life Sci. 1974 Feb 16;14(4):793–806. [PubMed] [Google Scholar]
  29. Nygren L. G., Olson L. A new major projection from locus coeruleus: the main source of noradrenergic nerve terminals in the ventral and dorsal columns of the spinal cord. Brain Res. 1977 Aug 19;132(1):85–93. doi: 10.1016/0006-8993(77)90707-7. [DOI] [PubMed] [Google Scholar]
  30. Parry O., Roberts M. H. The responses of motoneurones to 5-hydroxytryptamine. Neuropharmacology. 1980 Jun;19(6):515–518. doi: 10.1016/0028-3908(80)90020-9. [DOI] [PubMed] [Google Scholar]
  31. Reddy S. V., Maderdrut J. L., Yaksh T. L. Spinal cord pharmacology of adrenergic agonist-mediated antinociception. J Pharmacol Exp Ther. 1980 Jun;213(3):525–533. [PubMed] [Google Scholar]
  32. Shute C. C., Lewis P. R. Cholinergic and monoaminergic pathways in the hypothalamus. Br Med Bull. 1966 Sep;22(3):221–226. doi: 10.1093/oxfordjournals.bmb.a070477. [DOI] [PubMed] [Google Scholar]
  33. Simon E., Iriki M. Sensory transmission of spinal heat and cold sensitivity in ascending spinal neurons. Pflugers Arch. 1971;328(2):103–120. doi: 10.1007/BF00592439. [DOI] [PubMed] [Google Scholar]
  34. Simon E. Temperature regulation: the spinal cord as a site of extrahypothalamic thermoregulatory functions. Rev Physiol Biochem Pharmacol. 1974;(71):1–76. doi: 10.1007/BFb0027660. [DOI] [PubMed] [Google Scholar]
  35. Sinha J. N., Atkinson J. M., Schmitt H. Effects of clonidine and L-dopa on spontaneous and evoked splanchnic nerve discharges. Eur J Pharmacol. 1973 Oct;24(1):113–119. doi: 10.1016/0014-2999(73)90122-2. [DOI] [PubMed] [Google Scholar]
  36. Struyker Boudier H. A., Smeets G. W., Brouwer G. M., van Rossum J. M. Hypothalamic alpha adrenergic receptors in cardiovascular regulation. Neuropharmacology. 1974 Sep;13(9):837–846. doi: 10.1016/0028-3908(74)90039-2. [DOI] [PubMed] [Google Scholar]
  37. Wall P. D. The laminar organization of dorsal horn and effects of descending impulses. J Physiol. 1967 Feb;188(3):403–423. doi: 10.1113/jphysiol.1967.sp008146. [DOI] [PMC free article] [PubMed] [Google Scholar]
  38. Weight F. F., Salmoiraghi G. C. Adrenergic responses of Renshaw cells. J Pharmacol Exp Ther. 1966 Dec;154(3):391–397. [PubMed] [Google Scholar]
  39. Wünnenberg W., Brück K. Studies on the ascending pathways from the thermosensitive region of the spinal cord. Pflugers Arch. 1970;321(3):233–241. doi: 10.1007/BF00588444. [DOI] [PubMed] [Google Scholar]
  40. Yaksh T. L., Rudy T. A. Chronic catheterization of the spinal subarachnoid space. Physiol Behav. 1976 Dec;17(6):1031–1036. doi: 10.1016/0031-9384(76)90029-9. [DOI] [PubMed] [Google Scholar]
  41. Yeung J. C., Rudy T. A. Multiplicative interaction between narcotic agonisms expressed at spinal and supraspinal sites of antinociceptive action as revealed by concurrent intrathecal and intracerebroventricular injections of morphine. J Pharmacol Exp Ther. 1980 Dec;215(3):633–642. [PubMed] [Google Scholar]
  42. Young W. S., 3rd, Kuhar M. J. Noradrenergic alpha 1 and alpha 2 receptors: autoradiographic visualization. Eur J Pharmacol. 1979 Nov 16;59(3-4):317–319. doi: 10.1016/0014-2999(79)90299-1. [DOI] [PubMed] [Google Scholar]

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