Skip to main content
SpringerLink
Log in

Independent effects of cholinergic and serotonergic lesions on acetylcholine and serotonin release in the neocortex of the rat

  • Original Articles
  • Published:
Neurochemical Research Aims and scope Submit manuscript

Abstract

Rats received a unilateral lesion of the nucleus basalis magnocellularis (NBM) by infusion of ibotenic acid. In addition, the dorsal raphe nucleus was lesioned by infusion of 5,7-dihydroxytryptamine (5,7-DHT). The release of acetylcholine (ACh), choline, serotonin (5-HT) and 5-hydroxyindoleacetic acid (5-HIAA) was measured in the frontal neocortex by means of microdialysis. Lesions of the NBM, but not the raphe nucleus, reduced the release of ACh significantly (−47%). The release of 5-HT and 5-HIAA was reduced by raphe lesions (−44% and −79%), but not by NBM lesions. In no case did the combined lesion affect neurotransmitter release more than a single lesion. These results suggest that serotonergic projections from the dorsal raphe nucleus are not involved in tonic inhibition of ACh release in the neocortex.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Robinson, S. E. 1983. Effect of specific serotonergic lesions on cholinergic neurons in the hippocampus, cortex and striatum. Life Sci. 32:345–353.

    Google Scholar 

  2. Vizi, E. S., Harsing, L. G., and Zsilla, G. 1981. Evidence of the modulatory role of serotonin in acetylcholine release from striatal interneurons. Brain Res. 212:89–99.

    Google Scholar 

  3. Jackson, D., Stachowiak, M. K., Bruno, J. P., and Zigmond, M. J. 1988. Inhibition of striatal acetylcholine release by endogenous serotonin. Brain Res. 457:259–266.

    Google Scholar 

  4. Euvrard, C., Javoy, F., Herbet, A., and Glowinski, J. 1977. Effect of quipazine, a serotonin-like drug, on striatal cholinergic interneurons. Eur. J. Pharmacol. 41:281–289.

    Google Scholar 

  5. Ladinsky, H., Consolo, S., Peri, G., Crunelli, V., and Samanin, R. 1978. Pharmacological evidence for a serotonergic-cholinergic link in the striatum. Pages 615–627in Jenden, D. J. (ed), Cholinergic Mechanisms and Psychopharmacology. Plenum Press, New York.

    Google Scholar 

  6. Gillet, G., Ammor, S., and Fillion, G. 1985. Serotonin inhibits acetylcholine release from rat striatum slices: evidence for a presynaptic receptor-mediated effect. J. Neurochem. 45:1687–1691.

    Google Scholar 

  7. Barnes, J. M., Barnes, N. M., Costall, B., Naylor, R. J., and Tyers, M. B. 1989. 5-HT3 receptors mediate inhibition of acetylcholine release in cortical tissue. Nature. 338:762–763.

    Google Scholar 

  8. Maura, G., Fedele, E., and Raiteri, M. 1989. Acetylcholine release from rat hippocampal slices is modulated by 5-hydroxytryptamine. Eur. J. Pharmacol. 165:173–179.

    Google Scholar 

  9. Bianchi, C., Siniscalchi, A., and Beani, L. 1986. The influence of 5-hydroxytryptamine on the release of acetylcholine from guinea-pig ex vivo and in vitro. Neuropharmacology. 25:1043–1049.

    Google Scholar 

  10. Bianchi, C., Siniscalchi, A., and Beani, L. 1990. 5-HT1A agonists increase and 5-HT3 agonists decrease acetylcholine efflux from cerebral cortex of freely-moving guinea-pigs. Br. J. Pharmacol. 101:448–452.

    Google Scholar 

  11. Siniscalchi, A., Bianchi, A., and Beani, L. 1991. Influence of acute and chronic chlorimipramine treatment on the 5-HT receptor-mediated modulation of acetylcholine release from cerebral cortex of freely-moving guinea-pigs. Br. J. Pharmacol. 102:837–840.

    Google Scholar 

  12. Dekker, A. J., Connor, D. J., and Thal, L. J. 1991. The role of cholinergic projections from the nucleus basalis in memory. Neurosci. Biobehav. Rev. 15:299–317.

    Google Scholar 

  13. Olton, D. S., and Wenk, G. L. 1987. Dementia: animal models of the cognitive impairments produced by degeneration of the basal forebrain cholinergic system. Pages 941–953 in Meltzer, H. Y. (ed), Psychopharmacology: The Third Generation of Progress. Raven Press, New York.

    Google Scholar 

  14. Haroutunian, V., Santucci, A. C., and Davis, K. L. 1990. Implications of multiple transmitter system lesions for cholinomimetic therapy in Alzheimer's disease. Pages 333–343 in Aquilonius, S. M., and Gillberg, P. G. (eds), Progress in Brain Research. Vol 84. Elsevier, Amsterdam.

    Google Scholar 

  15. Sakurai, Y., and Wenk, G. L. 1990. The interaction of acetylcholinergic and serotonergic neural systems on performance in a continuous non-matching to sample task. Brain Res. 519:118–121.

    Google Scholar 

  16. Riekkinen, P., Sirvio, J., and Riekinnen, P. 1990. Interaction between raphe dorsalis and nucleus basalis magnocellularis in spatial learning. Brain Res. 527:342–345.

    Google Scholar 

  17. Vanderwolf, C. H. 1987. Near-total loss of ‘learning’ and ‘memory’ as a result of combined cholinergic and serotonergic blockade in the rat. Behav. Brain Res. 23:43–57.

    Google Scholar 

  18. Markowska, A. L., and Wenk, G. 1991. Serotonin influences the behavioral recovery of rats following nucleus basalis lesions. Pharmacol. Biochem. Behav. 38:731–737.

    Google Scholar 

  19. Nilsson, O. G., Strecker, R. E., Daszuta, A., and Bjorklund, A. 1988. Combined cholinergic and serotonergic denervation of the forebrain produces severe deficits in a spatial learning task in the rat. Brain Res. 453:235–246.

    Google Scholar 

  20. Paxinos, G., and Watson, C. 1986. The Rat Brain in Stereotaxic Coordinates. Academic Press, New York.

    Google Scholar 

  21. Herrera-Marschitz, M., Goiny, M., Utsumi, H., Ferre, S., Hakansson, L., Nordberg, A., and Ungerstedt, U. 1990. Effect of unilateral nucleus basalis lesion on cortical and striatal acetylcholine and dopamine release monitored in vivo with microdialysis. Neurosci. Lett. 110:172–179.

    Google Scholar 

  22. Mesulam, M.-M., Mufson, E. J., Wainer, B. H., and Levey, A. I. 1983. Central cholinergic pathways in the rat: an overview based on an alternative nomenclature (Ch1–Ch6). Neuroscience. 10:1185–1201.

    Google Scholar 

  23. Pearson, R. C. A., Gatter, K. C., Brodal, P., and Powell, T. P. S. 1983. The projection of the basal nucleus of Meynert upon the neocortex in the monkey. Brain Res. 259:132–136.

    Google Scholar 

  24. Dekker, A. J., Langdon, D. J., Gage, F. H., and Thal, L. J. 1991. NGF increases cortical acetylcholine release in rats with lesions of the nucleus basalis. Neuroreport. 2:577–580.

    Google Scholar 

  25. Parry, T. J., Carter, T. L., and McElligott, J. G. 1990. Physical and chemical considerations in the in vitro calibration of microdialysis probes for biogenic amine neurotransmitters and metabolites. J. Neurosci. Methods. 32:175–183.

    Google Scholar 

  26. Wu, C. F., Bertorelli, R., Sacconi, M., Pepeu, G., and Consolo, S. 1988. Decrease of brain acetylcholine release in aging freelymoving rats detected by microdialysis. Neurobiol. Aging 9:357–361.

    Google Scholar 

  27. Kalen, P., Strecker, R. E., Rosengren, E., and Bjorklund, A. 1988. Endogenous release of neuronal serotonin and 5-hydroxy-indoleacetic acid in the caudate-putamen of the rat as revealed by intracerebral dialysis coupled to high-performance liquid chromatography with fluorimetric detection. J. Neurochem. 51:1422–1435.

    Google Scholar 

  28. Nilsson, O. G., Kalen, P., Rosengren, E., and Bjorklund, A. 1990. Acetylcholine release in the rat hippocampus as studied by microdialysis is dependent on axonal impulse flow and increases during behavioural activation. Neuroscience. 36:325–338.

    Google Scholar 

  29. Langlais, P. J., Mair, R. G., Anderson, C. D., and McEntce, W. J. 1987. Monoamines and metabolites in cortex and subcortical structures: normal regional distribution and the effects of thiamine deficiency in the rat. Brain Res. 421:140–149.

    Google Scholar 

  30. Matson, W. R., Gamache, P. G., Beal, M. F., and Bird, E. D. 1987. EC array sensor concepts and data. Life Sci. 41:905–908.

    Google Scholar 

  31. Fonnum, F. 1969. Radiochemical microassays for the determination of choline acetyltransferase and acetylcholinesterase activities. Biochem. J. 115:456–479.

    Google Scholar 

  32. Lowry, O. H., Rosebrough, N. J., Farr, A. L., and Randall, R. J. 1951. Protein measurement with the Folin phenol reagent. J. Biol. Chem. 193:265–275.

    Google Scholar 

  33. Van de Kar, L. D., and Lorens, S. A. 1979. Differential serotonergic innervation of individual hypothalamic nuclei and other forebrain regions by the dorsal and median midbrain raphe nuclei. Brain Res. 162:45–54.

    Google Scholar 

  34. Cudennec, A., Duverger, D., Nishikawa, T., McRae-Degueurce, A., Mackenzie, E. T., and Scatton, B. 1988. Influence of ascending serotonergic pathways on glucose use in the conscious rat brain. I. Effects of electrolytic or neurotoxic lesions of the dorsal and/or median raphe nucleus. Brain Res. 444:214–226.

    Google Scholar 

  35. Murrin, L. C., and Kuhar, M. J. 1976. Activation of high-affinity choline uptake in vitro by depolarizing agents. Molec. Pharmacol. 12:1082–1090.

    Google Scholar 

  36. Baldwin, H. A., De Souza, R. J., Sarna, G. S., Murray, T. K., Green, A. R., and Cross, A. J. 1991. Measurements of tacrine and monoamines in brain by in vivo microdialysis argue against release of monoamines by tacrine at therapeutic doses. Br. J. Pharmacol. 103:1946–1950.

    Google Scholar 

  37. Hjorth, S., and Sharp, T. 1991. Effect of the 5-HT1A receptor agonist 8-OH-DPAT on the release of 5-HT in dorsal and median raphe-innervated rat brain regions as measured by in vivo microdialysis. Life Sci. 48:1779–1786.

    Google Scholar 

  38. Laferrere, B., and Wurtman, R. J. 1989. Effect of D-fenfluramine on serotonin release in brains of anesthetized rats. Brain Res. 504:258–263.

    Google Scholar 

  39. Sarkissian, C. F., Wurtman, R. J., Morse, A. N., and Gleason, R. 1990. Effects of fluoxetine or D-fenfluramine on serotonin release from, and levels in, rat frontal cortex. Brain Res. 529:294–301.

    Google Scholar 

  40. Dekker, A. J., and Thal, L. J. 1992. Effect of delayed treatment with nerve growth factor on choline acetyltransferase activity in the cortex of rats with lesions of the nucleus basalis magnocellularis: dose requirements. Brain Res. 584:55–63.

    Google Scholar 

  41. Martin, D. C., Watkins, C. A., Adams, R. J., and Nason, L. A. 1988. Anesthetic effects on 5-hydroxytryptamine uptake by rat brain synaptosomes. Brain Res. 455:360–365.

    Google Scholar 

  42. Martin, D. C., Introna, R. P., and Aronstam, R. S. 1990. Inhibition of neuronal 5-HT uptake by ketamine, but not halothane, involves disruption of substrate recognition by the transporter. Neurosci. Lett. 112:99–103.

    Google Scholar 

  43. Westerink, B. H. C., and De Vries, J. B. 1988. Characterization of in vivo dopamine release as determined by brain microdialysis after acute and subchronic implantations: methodological aspects. J. Neurochem. 51:683–687.

    Google Scholar 

  44. Moghaddam, B., Roth, R. H., and Bunney, B. S. 1990. Characterization of dopamine release in the rat medial prefrontal cortex as assessed by in vivo microdialysis: comparison to the striatum. Neuroscience. 36:669–676.

    Google Scholar 

  45. Westerink, B. H. C., Damsma, G., Rollema, H., De Vries, J. B., and Horn, A. S. 1987. Scope and limitations of in vivo brain dialysis: a comparison of its application to various neurotransmitter systems. Life Sci. 41:1763–1776.

    Google Scholar 

  46. Robinson, T. E., De Souza, R. J., Cross, A. J., and Green, A. R. 1989. The mechanism of tetrahydroaminoacridine-evoked release of endogenous 5-hydroxytryptamine and dopamine from rat brain tissue prisms. Br. J. Pharmacol. 98:1127–1136.

    Google Scholar 

  47. Semba, K., Reiner, P. B., McGeer, E. G., and Fibiger, H. C. 1988. Brainstem afferents to the magnocellular basal forebrain studied by axonal transport, immunohistochemistry, and electrophysiology in the rat. J. Comp. Neurol. 267:433–453.

    Google Scholar 

  48. Peroutka, S. J., Schmidt, A. W., Sleight, A. J., and Harrington, M. A. 1990. Serotonin receptor ‘families’ in the central nervous system: an overview. Ann. N.Y. Acad. Sci. 600:104–113.

    Google Scholar 

  49. Conn, P. J., and Sanders-Bush, E., 1986. Regulation of serotoninstimulated phosphoinositide hydrolysis: relation to the 5-HT2 binding site. J. Neurosci. 6:3669–3675.

    Google Scholar 

  50. Scarth, B. J., Jhamandas, K., Boegman, R. J., Beninger, R. J., and Reynolds, J. N. 1989. Cortical muscarinic receptor function following quinolinic acid-induced lesion of the nucleus basalis magnocellularis. Exp. Neurol. 103:158–164.

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Neurosciences, University of California and Neurology Service, VA Medical Center, 3350 La Jolla Village Drive, 92161, San Diego, CA

    Ad J. Dekker & Leon J. Thal (Dr)

Authors
  1. Ad J. Dekker
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Leon J. Thal
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Dekker, A.J., Thal, L.J. Independent effects of cholinergic and serotonergic lesions on acetylcholine and serotonin release in the neocortex of the rat. Neurochem Res 18, 277–283 (1993). https://doi.org/10.1007/BF00969083

Download citation

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF00969083

Key Words

Search

Navigation