Skip to main content
SpringerLink
Log in

Serotonin (5-HT) release in the dorsal raphé and ventral hippocampus: Raphé control of somatodendritic and terminal 5-HT release

  • Published:
Journal of Neural Transmission Aims and scope Submit manuscript

Summary

Somatodendritic and terminal release of serotonin (5-HT) was investigated by simultaneously measuring extracellular concentrations of 5-HT, 5-hydroxyindole-3-acetic acid (5-HIAA) and homovanillic acid (HVA) in the dorsal raphé and ventral hippocampus in freely moving rats. Perfusion of tetrodotoxin (TTX, 1μM and 10μM) into the dorsal raphé simultaneously decreased dorsal raphé and hippocampal 5-HT release. However, following TTX perfusion into the hippocampus (10μM), hippocampal 5-HT release was profoundly reduced but dorsal raphé 5-HT remained unchanged.

Systemic injections with the 5-HT1a agonist, buspirone (1.0–5.0mg/kg, i.p.) decreased 5-HT and 5-HIAA and increased HVA concentrations in the dorsal raphé and in the hippocampus. The decreases in raphé and hippocampal 5-HT induced by systemic buspirone were antagonized in rats pretreated with 1.OmM (−) pindolol, locally perfused into the dorsal raphé. Local dorsal raphé perfusion of (−) pindolol alone (0.01–1.0mM) increased dorsal raphé 5-HT and concomitantly induced a small increase in hippocampal 5-HT. Buspirone perfusion into the dorsal raphé did not change (10 nM, 100nM), or produced a small increase (1.0mM) in raphé 5-HT, without changing hippocampal 5-HT.

These data provide evidence that 5-HT release in the dorsal raphé is dependent on the opening of fast activated sodium channels and that dorsal raphé 5-HT1a receptors control somatodendritic and hippocampal 5-HT release.

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

  • Adell A, Hjorth S (1991) 8-OH-DPAT perfusion into the dorsal raphe nucleus of the freely moving rat decreased terminal but not somatodendritic 5-HT release. Soc Neurosci Abstr 17: 1542

    Google Scholar 

  • Adell A, Carceller A, Artigas F (1993) In vivo brain dialysis study of the somatodendritic release of serotonin in the raphé nuclei of the rat: effects of 8-hydroxy-2-(di-n-propylamino)tetralin. J Neurochem 60: 1673–1681

    Google Scholar 

  • Agneter E, Singer EA (1993) Autoreceptor-mediated control of 5-hydroxytryptamine release from medullary raphe nuclei in the freely moving rat. Naunyn Schmiedebergs Arch Pharmacol 347: 493

    Google Scholar 

  • Azmitia EC, Segal M (1978) An autoradiographic analysis of the differential ascending projections of the dorsal and median raphe nuclei in the rat. J Comp Neurol 179: 641–668

    Google Scholar 

  • Baraban JM, Aghajanian GK (1981) Noradrenergic innervation of serotonergic neurons in the dorsal raphe: demonstration by electron microscopic autoradiograph. Brain Res 204: 1–11

    Google Scholar 

  • Becquet D, Faudon M, Hery F (1990) The role of serotonin release and autoreceptors in the dorsalis raphe nucleus in the control of serotonin release in the cat caudate nucleus. Neuroscience 39: 639–647

    Google Scholar 

  • Blier P, DeMontigny C (1987) Modification of 5-HT neuron properties by sustained administration of the 5-HT1A agonist gepirone: electrophysiological studies in the rat brain. Synapse 1: 470–480

    Google Scholar 

  • Bonvento G, Scatton B, Claustre Y, Rouquier L (1992) Effect of local injection of 8-OH-DPAT into the dorsal or median raphe nuclei on extracellular levels of serotonin in serotonergic projection areas in the rat brain. Neurosci Lett 137: 101–104

    Google Scholar 

  • Bosker F, Klompmakers A, Westenberg H (1994) Extracellular 5-Hydroxytryptamine in median raphé nucleus of the conscious rat is decreased by nanomolar concentrations of 8-hydroxy-2-(di-n-propylamino) tetralin and is sensitive to tetrodotoxin. J Neurochem 63: 2165–2171

    Google Scholar 

  • Carboni E, Di Chiara G (1989) Serotonin release estimated by transcortical dialysis in freely-moving rats. Neuroscience 32: 637–645

    Google Scholar 

  • Chazal G, Ralston III HJ (1987) Serotonin-containing structures in the nucleus raphe dorsalis of the cat: an ultrastructural analysis of dendrites, presynaptic dendrites, and axon terminals. J Comp Neurol 259: 317–329

    Google Scholar 

  • Cimino M, Ponzio F, Achilli G, Vantini G, Perego C, Algeri S, Garattini S (1983) Dopaminergic effects of buspirone, a novel anxiolytic agent. Biochem Pharmacol 32: 1069–1074

    Google Scholar 

  • Claustre Y, Rouquier L, Bonvento G, Benavides J, Scatton B (1991) In vivo regulation of serotonin release by 5-HT autoreceptors and alphal-adrenoceptors in the rat and guinea pig brain. In: Rollema H, Westerink B, Jan Drijfhout W (eds) Monitoring molecules in neuroscience. University Center for Pharmacy, Groningen, The Netherlands, pp 247–249

    Google Scholar 

  • Descarries L, Watkins KC, Garcia S, Beaudet A (1982) The serotonin neurons in nucleus raphe dorsalis of adult rat: a light and electron microscope radioautographic study. J Comp Neurol 207: 239–254

    Google Scholar 

  • Gehlbach G, VanderMaelen CP (1987) (−) Pindolol blocks the inhibitory effect of gepirone, a 5-HT1A agonist, on the firing of serotonergic dorsal raphe neurons in the rat brain slice. Soc Neurosci Abstr 13: 1649

    Google Scholar 

  • Hery F, Faudon M, Fueri C (1986) Release of serotonin in structures containing serotonergic nerve cell bodies: dorsalis raphe nucleus and nodose ganglia of the cat. Ann NY Acad Sci 473: 239–255

    Google Scholar 

  • Hery F, Faudon M, Ternaux J-P (1982) In vivo release of serotonin in two raphe nuclei (raphe dorsalis and magnus) of the cat. Brain Res Bull 8: 123–129

    Google Scholar 

  • Hjorth S, Magnusson T (1988) The 5-HT1A receptor agonist, 8-OH-DPAT, preferentially activates cell body 5-HT autoreceptors in rat brain in vivo. Naunyn Schmiedebergs Arch Pharmacol 338: 463–471

    Google Scholar 

  • Hjorth S, Sharp T (1993) In vivo microdialysis evidence for central serotonin1A and serotonin1B autoreceptor blocking properties of the beta adrenoceptor antagonist (−) penbutolol. J Pharmacol Exp Ther 265: 707–712

    Google Scholar 

  • Hoyer D (1988) Functional correlates of serotonin 5-HT1 recognition sites. J Recept Res 8: 59–81

    Google Scholar 

  • Hutson PH, Sarna GS, O'Connell MT, Curzon G (1989) Hippocampal 5-HT synthesis and release in vivo is decreased by infusion of 8-OHDPAT into the nucleus raphe dorsalis. Neurosci Lett 100: 276–280

    Google Scholar 

  • Invernizzi R, Carli M, Di Clemente A, Samanin R (1991) Administration of 8-hydroxy-2-(Di-n-propylamino)tetralin in raphe nuclei dorsalis and medianus reduces serotonin synthesis in the rat brain: differences in potency and regional sensitivity. J Neurochem 56: 243–247

    Google Scholar 

  • Kalén P, Strecker RE, Rosengren E, Bjorklund A (1988) Endogenous release of neuronal serotonin and 5-hydroxyindoleacetic 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 

  • Matos FF, Rollema H, Basbaum AI (1990) Characterization of monoamine release in the lateral hypothalamus of awake, freely moving rats using in vivo microdialysis. Brain Res 528: 39–47

    Google Scholar 

  • Matos FF, Rollema H, Basbaum AI (1992) Simultaneous measurement of extracellular morphine and serotonin in brain tissue and CSF by microdialysis in awake rats. J Neurochem 58: 1773–1781

    Google Scholar 

  • McMillen BA, Matthews RT, Sanghera MK, Shepard PD, German DC (1983) Dopamine receptor antagonism by the novel anti-anxiety drug, buspirone. J Neurosci 3: 733–738

    Google Scholar 

  • Moore RY, Halaris AE (1975) Hippocampal innervation by serotonin neurons of the midbrain raphe in the rat. J Comp Neurol 164: 171–184

    Google Scholar 

  • Nomikos GG, Arborelius L, Svensson TH (1992) The novel 5-HT1A receptor antagonist (S)-UH-301 prevents (R)-8-OH-DPAT-induced decrease in interstitial concentrations of serotonin in the rat hippocampus. Eur J Pharmacol 216: 373–378

    Google Scholar 

  • Paxinos G, Watson C (1986) The rat brain in stereotaxic coordinates. Academic Press, Orlando, FL

    Google Scholar 

  • Pecci-Saavedra J, Brusco A, Peressini S, Olivia D (1986) A new case for a presynaptic role of dendrites: an immunocytochemical study of the n. raphé dorsalis. Neurochem Res 11: 997–1009

    Google Scholar 

  • Piercey MF, Smith MW, Lum-Ragan JT (1994) Excitation of noradrenergic cell firing by 5-hydroxytryptaminelA agonists correlates with dopamine antagonist properties. J Pharmacol Exp Ther 268: 1297–1303

    Google Scholar 

  • Santiago M, Westerink BHC (1992) Simultaneous recording of the release of nigral and striatal dopamine in the awake rat. Neurochem Int 20: 107S-110S

    Google Scholar 

  • Sharp T, Bramwell SR, Grahame-Smith DG (1989a) 5-HT1 agonists reduce 5-hydrox-ytryptamine release in rat hippocampus in vivo as determined by brain microdialysis. Br J Pharmacol 96: 283–290

    Google Scholar 

  • Sharp T, Bramwell SR, Clark D, Grahame-Smith DG (1989b) In vivo measurement of extracellular 5-hydroxytryptamine in hippocampus of the anaesthetized rat using microdialysis: changes in relation to 5-hydroxytryptaminergic neuronal activity. J Neurochem 53: 234–240

    Google Scholar 

  • Sharp T, Bramwell SR, Hjorth S, Grahame-Smith DG (1989c) Pharmacological characterization of 8-OH-DPAT-induced inhibition of rat hippocampal 5-HT release in vivo as measured by microdialysis. Br J Pharmacol 98: 989–997

    Google Scholar 

  • Sharp T, Bramwell SR, Grahame-Smith DG (1990) Release of endogenous 5-hydroxytryptamine in rat ventral hippocampus evoked by electrical stimulation of the dorsal raphe nucleus as detected by microdialysis: sensitivity to tetrodotoxin, calcium and calcium antagonists. Neuroscience 39: 629–637

    Google Scholar 

  • Sprouse JS, Aghajanian GK (1986) (−)-Propranolol blocks the inhibition of serotonergic dorsal raphe cell firing by 5-HT1A selective agonists. Eur J Pharmacol 128: 295–298

    Google Scholar 

  • Sprouse JS, Aghajanian GK (1987) Electrophysiological responses of serotoninergic dorsal raphe neurons to 5-HT1A and 5-HT1B agonists. Synapse 1: 3–9

    Google Scholar 

  • Starkey SJ, Skingle M (1994) 5-HT1D as well as 5-HT1A autoreceptors modulate 5-HT release in the guinea-pig dorsal raphé nucleus. Neuropharmacology 33: 393–402

    Google Scholar 

  • VanderMaelen CP, Braselton JP (1992) (−) Penbutolol antagonizes 8-OH-DPAT-induced inhibition of rat 5-hydroxytryptaminergic dorsal raphé neurons. Br J Pharmacol 107 [Suppl] 2P

  • VanderMaelen CP, Matheson GK, Wilderman RC, Patterson LA (1986) Inhibition of serotonergic dorsal raphe neurons by systemic and iontophoretic administration of buspirone, a non-benzodiazepine anxiolytic drug. Eur J Pharmacol 129: 123–130

    Google Scholar 

  • Wei LJ, Lachin JM (1984) Two sample asymptotically distribution free tests for incomplete multivariate observations. J Am Stat Assoc 39: 653–661

    Google Scholar 

Download references

Author information

Author notes

  1. F. F. Matos

    Present address: Department of Neuropharmacology, CNS Drug Discovery, Bristol-Myers Squibb Pharmaceutical Research Institute, Wallingford, CT, USA

Authors and Affiliations

  1. Department of Neuropharmacology, CNS Drug Discovery, Bristol-Myers Squibb Pharmaceutical Research Institute, Wallingford, CT, USA

    C. Urban & F. D. Yocca

Authors
  1. F. F. Matos
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. C. Urban
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. F. D. Yocca
    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

Matos, F.F., Urban, C. & Yocca, F.D. Serotonin (5-HT) release in the dorsal raphé and ventral hippocampus: Raphé control of somatodendritic and terminal 5-HT release. J. Neural Transmission 103, 173–190 (1996). https://doi.org/10.1007/BF01292626

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF01292626

Keywords

Search

Navigation