Neurochemical Research

, Volume 17, Issue 5, pp 401–407 | Cite as

Regulation of nucleus accumbens dopamine release by the dorsal raphe nucleus in the rat

  • K. Yoshimoto
  • W. J. McBride
Original Articles


The effects of microinfusingl-glutamate, serotonin (5-HT), (±)-8-hydroxy-2-(di-N-propylamino) tetralin (8-OH DPAT; a 5-HT1A agonist), and muscimol (a GABAA agonist) into the dorsal raphe nucleus on the extracellular levels of 5-HT, dopamine (DA) and their metabolites in the nucleus accumbens were studied in unanesthetized, freely moving, adult male Wistar rats, using the technique of microdialysis coupled with small-bore HPLC. Administration of 0.75 μgl-glutamate produced a 25–50% increase (P<0.05) in the extracellular levels of both 5-HT and DA. On the other hand, infusion of 8-OH DPAT and, to a lesser extent, 5-HT produced a significant (P<0.05) decrease in the extracellular levels of both 5-HT and DA. Muscimol (0.25 or 0.50 μg) had little effect on the extracellular concentrations of 5-HT or DA following its administration. In general, the extracellular levels of the major metabolites of 5-HT and DA in the nucleus accumbens were not altered by microinfusion of any of the agents. The data indicate that (a) the 5-HT neurons projecting to the nucleus accumbens from the dorsal raphe nucleus can be activated by excitatory amino acid receptors and inhibited by stimulation of 5-HT1A autoreceptors, and (b) the dorsal raphe nucleus 5-HT neuronal system may regulate the ventral tegmental area DA projection to the nucleus accumbens.

Key Words

In vivo microdialysis dopamine serotonin nucleus accumbens dorsal raphe nucleus microinfusions 


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  1. 1.
    Phillips, A. G. 1984. Brain reward circuitry: a case for separate systems. Brain Res. Bull. 12:195–201.Google Scholar
  2. 2.
    Wise, R. A., and Bozarth, M. A. 1984. Brain reward circuitry: four circuit elements “wired” in apparent series. Brain Res. Bull. 12:203–208.Google Scholar
  3. 3.
    Fibiger, H. C., and Phillips, A. G. 1986. Reward, motivation, cognition: psychobiology of mesotelencephalic dopamine systems. P Pages 647–675,in Bloom, F. E. (ed.), Handbook of Physiology, Section 1: The Nervous System, Vol. IV. American Physiological Society, Baltimore.Google Scholar
  4. 4.
    Koob, G. F., and Bloom, F. E. 1988. Cellular and molecular mechanisms of drug dependence. Science 242:715–723.Google Scholar
  5. 5.
    DiChiara, G., and Imperato, A. 1988. Drugs abused by humans preferentially increase synaptic dopamine concentrations in the mesolimbic system of freely moving rats. Proc. Natl. Acad. Sci. (USA) 85:5274–5278.Google Scholar
  6. 6.
    Moore, R. Y., Halaris, A. E., and Jones, B. E. 1978. Serotonin neurons of the midbrain raphe: ascending projections. J. Comp. Neurol. 180:417–437.Google Scholar
  7. 7.
    Phillipson, O. T. 1979. Afferent projections of the ventral tegmental area of Tsai and interfascicular nucleus: a horseradish peroxidase study in the rat. J. Comp. Neurol. 187:117–144.Google Scholar
  8. 8.
    Parent, A., Descarries, L., and Beaudet, A. 1981. Organization of ascending serotonin systems in the adult rat brain. A radioautographic study after intraventricular administration of [3H]5-hydroxytryptamine. Neurosci. 6:115–138.Google Scholar
  9. 9.
    Herve D., Pickel, V. M., Hoh, T. H., and Beaudet, A. 1987. Serotonin axon terminals in the ventral tegmental area of the rat: fine structure and synaptic input to dopaminergic neurons. Brain Res. 435:71–83.Google Scholar
  10. 10.
    Saavedra, J. M. Brownstein, M., and Palkovits, M. 1974. Serotonin distribution in the limbic system of the rat. Brain Res. 79:437–441.Google Scholar
  11. 11.
    Beart, P. M., and McDonald, D. 1982. 5-Hydroxytryptamine and 5-hydroxytryptaminergic-dopaminergic interactions in the ventral tegmental area of rat brain. J. Pharm. Pharmacol. 34:591–593.Google Scholar
  12. 12.
    Herve, D., Simon, H., Blanc, G., Kisoprawski, A. LeMoal, M., Glowinski, J., and Tassin, J. P. 1979. Increased utilization of dopamine in the nucleus accumbens but not in the cerebral cortex after dorsal raphe lesion in the rat. Neurosci. Lett. 15:127–133.Google Scholar
  13. 13.
    Ugedo, L., Grenhoff, J., and Svensson, T. H. 1989. Ritanserin, a 5-HT2 receptor antagonist, activates midbrain dopamine neurons by blocking serotonergic inhibition. Psychopharmacology 98:45–50.Google Scholar
  14. 14.
    Redgrave, P., and Horrell, R. I. 1976. Potentiation of central reward by localized perfusion of acetylcholine and 5-hydroxytryptamine. Nature 262:305–307.Google Scholar
  15. 15.
    Guan, X.-M., and McBride, W. J. 1989. Serotonin microinfusion into the ventral tegmental area increases accumbens dopamine release. Brain Res. Bull. 23:541–547.Google Scholar
  16. 16.
    Paxinos, G., and Watson, C. 1986. The rat brain in stereotaxic coordinates. Second Edition, Academic Press, New York.Google Scholar
  17. 17.
    Murphy, J. M., McBride, W. J., Lumeng, L., and Li, T.-K. 1982. Regional brain levels of monoamines in alcohol-preferring and-nonpreferring lines of rats. Pharmacol. Biochem. Behav. 16:145–149.Google Scholar
  18. 18.
    Murphy, J. M., McBride, W. J., Lumeng, L., and Li, T.-K. 1983. Monoamine and metabolite levels in CNS regions of the P line of alcohol-preferring rats after acute and chronic ethanol treatment. Pharmacol. Biochem. Behav. 19:849–856.Google Scholar
  19. 19.
    Sainati, S. M., and Lorens, S. A. 1982. Intra-raphe muscimol induced hyperactivity depends on ascending serotonin projections. Pharmacol. Biochem. Behav. 17:973–986.Google Scholar
  20. 20.
    Klitenick, M. A., and Wirtshafter, D. 1988. Comparative studies of the ingestive behaviors produced by microinjections of muscimol into the midbrain raphe nuclei or the ventral tegmental area of the rat. Life Sci. 42:775–782.Google Scholar
  21. 21.
    Steinbusch, H. W. M., and Nieuwenhuys, R. 1983. The raphe nuclei of the brain stem: a cytoarchitectonic and immunohistochemical study. Pages 131–208,in Emson, P. C. (ed.), Chemical Neuroanatomy. Raven Press, New York.Google Scholar
  22. 22.
    Kalen, P., Karlson, M., and Wiklund, L. 1985. Possible excitatory amino acid afferents to nucleus raphe dorsalis of the rat investigated with retrograde wheat germ agglutinin andd-[3H]aspartate tracing. Brain Res. 360:385–297.Google Scholar
  23. 23.
    Kalen, P., Strecker R. E., Rosegren, E. and Bjorklund, A. 1989. Regulation of striatal serotonin release by the lateral habenula-dorsal raphe pathway in the rat as demonstrated by in vivo microdialysis: role of excitatory amino acids and GABA. Brain Res. 492:187–202.Google Scholar
  24. 24.
    Hjorth, S. Carlsson, A., Lindburg, P., Sanchez, D., Wikstrom, I., Arvidsson, L. E., Hacksell, U., and Nilsson, J. L. G. 1982. 8-Hydroxy-2-(di-n-propylamino) tetralin, 8-OH DPAT, a potent and selective simplified ergot congener with central 5-HT-receptor stimulating activity. J. Neural Transm. 55:169–188.Google Scholar
  25. 25.
    Middlemiss, D. N., and Fozard, J. R. 1983. 8-Hydroxy-2-(di-n-propylamino) tetralin discriminates between subtypes of the 5-HT1 recognition sites. Eur. J. Pharmacol. 90:151–153.Google Scholar
  26. 26.
    Weissmann-Nanopoulos, D., Mach, E., Magre, J. E., Demassy, Y., and Pujol, J. F. 1985. Evidence for the localisation of 5-HT1A binding sites on serotonin containing neurons in the raphe dorsalis and raphe centralis nuclei of the rat brain. Neurochem. Int. 7:1061–1072.Google Scholar
  27. 27.
    Verge, D., Daval, G., Patey, A., Gozlan, H., El Mestikawy, S., and Hamon, M. 1985. Presynaptic 5-HT autoreceptors on serotonergic cell bodies and/or dendrites but not terminals are of the 5-HT1A subtype. Eur. J. Pharmacol. 113:463–464.Google Scholar
  28. 28.
    Sprouse, J. S., and Aghajanian, G. K. 1987. Electrophysiological responses of serotonergic dorsal raphe neurons to 5-HT1A and 5-HT1B agonists. Synapse 1:3–9.Google Scholar
  29. 29.
    Sinton, C. M., and Fallon, S. C. 1988. Electrophysiological evidence for a functional differentiation between subtypes of the 5-HT1 receptor. Eur. J. Pharmacol. 157:173–181.Google Scholar
  30. 30.
    Higgins, G. A., Bradbury, A. J., Jones, B. J., and Oakley, N. R. 1988. Behavioural and biochemical consequences following activation of 5-HT1-like and GABA receptors in the dorsal raphe nucleus of the rat. Neuropharmacol. 27:993–1001.Google Scholar
  31. 31.
    Hjorth, S., and Magnusson, T. 1988. The 5-HT1A receptor agonist, 8-OH-DPAT, preferentially activates cell body 5-HT autoreceptors in rat brain in vivo. N.-Sch. Arch. Pharmacol. 338:463–471.Google Scholar
  32. 32.
    Hutson, P. H., Sarna, G. S., O'Connell, M. T., and Curzon, G. 1989. Hippocampal 5-HT synthesis and release in vivo is decreased by infusion of 8-OH DPAT into the nucleus raphe dorsalis. Neurosci. Lett. 100:276–280.Google Scholar
  33. 33.
    Hillegaart, V., Hjorth, S., and Ahlenius, S. 1990. Effects of 5-HT and 8-OH-DPAT on forebrain monoamine synthesis after local application into the median and dorsal raphe nuclei of the rat. J. Neural Transm. 81:131–145.Google Scholar
  34. 34.
    Imperato, A., and Angelucci, L. 1989. 5-HT3 receptors control dopamine release in the nucleus accumbens of freely moving rats. Neurosci. Lett. 101:214–217.Google Scholar
  35. 35.
    Jiang, L. H., Ashby Jr., C. R., Kasser., R. J., and Wang, R. Y. 1990. The effect of intraventricular administration of the 5-HT3 receptor agonist 2-methyl serotonin on the release of dopamine in the nucleus accumbens: an in vivo chronocoulometric study. Brain Res. 513:156–160.Google Scholar
  36. 36.
    Blandina, P., Goldfarb, J., Craddock-Royal, B., and Green, J. P. 1989. Release of endogenous dopamine by stimulation of 5-hydroxytryptamine3 receptors in rat striatum. J. Pharmacol. Exp. Ther. 251:803–809.Google Scholar
  37. 37.
    Nishikawa, T., and Scatton, B. 1983. Evidence for a GABAergic inhibitory influence on serotonergic neurons originating from the dorsal raphe. Brain Res. 279:325–329.Google Scholar
  38. 38.
    Scatton, B., Serrano, A., and Nishikawa, T. 1985. GABA mimetics decrease extracellular concentrations of 5-HIAA (as measured by in vivo voltammetry) in the dorsal raphe of the rat. Brain Res. 341:372–376.Google Scholar
  39. 39.
    Laitinen, K., Crawley, J. N., Mefford, I. N., and DeWitte, Ph. 1990. Neurotensin and cholecystokinin microinjected into the ventral tegmental area modulate microdialysate concentrations of dopamine and metabolites in the posterior nucleus accumbens. Brain Res. 523:342–346.Google Scholar

Copyright information

© Plenum Publishing Corporation 1992

Authors and Affiliations

  • K. Yoshimoto
    • 1
  • W. J. McBride
    • 1
  1. 1.Departments of Psychiatry and Biochemistry and Molecular Biology, Institute of Psychiatric ResearchIndiana University School of MedicineIndianapolis

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