Skip to main content
SpringerLink
Log in

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

  • Full Papers
  • Published:
Journal of Neural Transmission / General Section JNT Aims and scope Submit manuscript

Summary

5-HT (10 and 40 Μg) and 8-OH-DPAT (1 and 5 Μg) were locally applied into the dorsal or median raphe nuclei in awake, unrestrained, rats. All animals were also treated with the 5-HTP and DOPA decarboxylase inhibitor NSD-1015, 100mg kg−1 SC, 30 min before decapitation. 5-HT or 8-OH-DPAT were administered 5 min before NSD-1015. The regional brain in vivo rate of tyrosine and tryptophan hydroxylase activity was estimated by measuring the accumulation of DOPA and 5-HTP. The following brain regions were sampled: neocortex, hippocampus, dorso-lateral neostriatum, ventro-medial neostriatum, nucleus accumbens, olfactory tubercle, globus pallidus, septum and the amygdala.

Compared to normal controls, there were small and inconsistent effects on forebrain 5-HTP accumulation by saline injections into the dorsal or the median raphe (an increase in 3 out of 36 experiments), whereas strong effects by the injection procedure were noted on forebrain DOPA accumulation (an increase in 15 out of 36 experiments).

Injections of 5-HT (same effect by 10 or 40 Μg) into the dorsal raphe, produced a decrease in 5-HTP accumulation in all forebrain areas except for the hippocampus and the septum, whereas no effects were seen in any area after median raphe injections. In contrast, 8-OH-DPAT preferentially produced a decrease in forebrain 5-HTP accumulation after median raphe injections and less, but statistically significant effects by dorsal raphe injections. The 8-OH-DPAT injection into the median raphe primarily affected limbic forebrain areas (hippocampus, nucleus accumbens, ventro-medial neostriatum, amygdala and the septum).

This dissociation of the effects of 5-HT and 8-OH-DPAT on forebrain 5-HT synthesis after local application into the dorsal or the median raphe strongly supports the contention of heterogeniety in the brain 5-HT receptor population in terms of receptor subtypes and/or receptor regulation.

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

  • Ahlenius S, Hillegaart V, Wijkström A (1989) Evidence for selective inhibition of limbic forebrain dopamine synthesis by 8-OH-DPAT in the rat. Naunyn-Schmiedebergs Arch Pharmacol 339: 551–556

    Google Scholar 

  • Ahlenius S, Larsson K (1985) Antagonism by lisuride and 8-OH-DPAT of 5-HTP-induced prolongation of the performance of male rat sexual behavior. Eur J Pharmacol 110: 379–381

    Google Scholar 

  • Ahlenius S, Larsson K (1989) New aspects of the serotonergic modulation of male rat sexual behavior. In: Bevan P, Cools AR, Archer T (eds) Behavioral pharmacology of 5-HT. Lawrence Erlbaum, Hillsdale, pp 35–53

    Google Scholar 

  • Ahlenius S, Larsson K, Svensson L, Hjorth S, Carlsson A, Lindberg P, Wikström H, Sanchez D (1981) Effects of a new type of 5-HT receptor agonist on male rat sexual behavior. Pharmacol Biochem Behav 15: 785–792

    Google Scholar 

  • Arvidsson L-E, Hacksell U, Nilsson JLG, Hjorth S, Carlsson A, Lindberg P, Sanchez D, Wikström H (1981) 8-Hydroxy-2-(di-n-propylamino)tetralin, a new centrally acting 5-hydroxytryptamine receptor agonist. J Med Chem 24: 921–923

    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 

  • Bobillier P, Seguin S, Degueurce A, Lewis BD, Pujol JF (1979) The efferent connections of the nucleus raphe centralis superior in the rat as revealed by radioautography. Brain Res 166: 1–8

    Google Scholar 

  • Carlsson A, Davis JN, Kehr W, Lindqvist M, Atack CV (1972) Simultaneous measurement of tyrosine and tryptophan hydroxylase activities in brain in vivo using an inhibitor of the aromatic amino acid decarboxylase. Naunyn-Schmiedebergs Arch Pharmacol 275: 153–168

    Google Scholar 

  • Carlsson M, Eriksson E (1986) A central serotonin receptor agonist, 8-hydroxy-2-(di-n-proylamino)tetralin, has different effects on prolactin secretion in male and female rats. Acta Pharmacol Toxicol 58: 297–302

    Google Scholar 

  • Colino A, Halliwell JV (1987) Differential modulation of three separate K-conductances in hippocampal CA1 neurons by serotonin. Nature 328: 73–77

    Google Scholar 

  • Conrad LCA, Leonard CM, Pfaff DW (1974) Connections of the median and dorsal raphe nuclei in the rat: an autoradiographic and degeneration study. J Comp Neurol 156: 179–206

    Google Scholar 

  • Costain DW, Green AR (1978) \-Adrenoceptor antagonists inhibit the behavioural responses of rats to increased brain 5-hydroxytryptamine. Br J Pharmacol 64: 193–200

    Google Scholar 

  • DeMontigny C, Blier P, Chaput Y (1984) Electrophysiologically-identified serotonin receptors in the rat CNS: effect of antidepressant treatment. Neuropharmacology 23: 1511–1520

    Google Scholar 

  • Dourish CT, Hutson PH, Curzon G (1985) Low doses of the putative serotonin agonist 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) elicit feeding in the rat. Psychopharmacology 86: 197–204

    Google Scholar 

  • Engel JA, Hjorth S, Svensson K, Carlsson A, Liljequist S (1984) Anticonflict effect of the putative serotonin receptor agonist 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT). Eur J Pharmacol 105: 365–368

    Google Scholar 

  • 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

    Google Scholar 

  • Gerber R, Barbaz BJ, Martin LL, Neale R, Williams M, Liebman JM (1985) Antagonism ofL-5-hydroxytryptophan-induced head twitching in rats by lisuride: a mixed 5-hydroxytryptamine agonist-antagonist. Neurosci Lett 60: 207–213

    Google Scholar 

  • Goodwin GM, Green AR (1985) A behavioural and biochemical study in mice and rats of putative agonists and antagonists for 5-HT1 and 5-HT2 receptors. Br J Pharmacol 84: 743–753

    Google Scholar 

  • Green AR, Goodwin GM (1987) The pharmacology of the hypothermic response of rodents to 8-OH-DPAT administration and the effects of psychotropic drug administration on this response. In: Dourish CT, Ahlenius S, Hutson PH (eds) Brain 5-HT1A receptors. Ellis Horwood, Chichester, pp 161–176

    Google Scholar 

  • Green AR, Grahame-Smith DG (1976) (−)Propranolol inhibits the behavioural responses of rats to increased 5-hydroxytryptamine in the central nervous system. Nature 262: 594–596

    Google Scholar 

  • Hamon M, Emerit MB, El Mestikawy S, Verge D, Daval G, Marquet A, Gozlan H (1987) Pharmacological, biochemical and functional properties of 5-HT1A receptor binding sites labelled by [3H]8-hydroxy-2-(di-n-propylamino)tetralin in the rat brain. In: Dourish CT, Ahlenius S, Hutson PH (eds) Brain 5-HT1A receptors. Ellis Horwood, Chichester, pp 34–51

    Google Scholar 

  • Hillegaart V, Ahlenius S, Larsson K (1988) Different roles of the median and dorsal raphe nuclei in rat serotonergic motor functions. Neurochem Int 13 (S1): 126

    Google Scholar 

  • Hillegaart V, Ahlenius S, Larsson K (1989) Effects of local application of 5-HT into the median and dorsal raphe nuclei on male rat sexual and motor behavior. Behav Brain Res 33: 279–286

    Google Scholar 

  • Hillegaart V, Hjorth S (1989) Median raphe, but not dorsal raphe, application of the 5-HT1A agonist 8-OH-DPAT stimulates rat motor activity. Eur J Pharmacol 160: 303–307

    Google Scholar 

  • Hjorth S (1985) Hypothermia in the rat induced by the potent serotonergic agent 8-OH-DPAT. J Neural Transm 61: 131–135

    Google Scholar 

  • Hjorth S, Carlsson A, Lindberg P, Sanchez D, Wikström H, Arvidsson L-E, Hacksell U, Nilsson JLG (1982) 8-Hydroxy-2-(di-n-propylamino)tetralin, 8-OH-DPAT, a potent an selective simplified ergot congener with central 5-HT-receptor stimulating activity. J Neural Transm 55: 169–188

    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 

  • Hornung J-P, Fritschy J-M (1988) Serotonergic system in the brain stem of the marmoset: a combined immunocytochemical and three-dimensional reconstruction study. J Comp Neurol 270: 471–487

    Google Scholar 

  • Hoyer D, Engel G, Kalkman HO (1985) Molecular pharmacology of 5-HT1 and 5-HT2 recognition sites in rat and pig brain membranes: radioligand binding studies with [3H]5-HT, [3H]8-OH-DPAT, (−)[125I] iodocyanopindolol, [3H]mesulergine and [3H]ketanserin. Eur J Pharmacol 118: 13–23

    Google Scholar 

  • Hutson PH, Dourish CT, Curzon G (1988) Evidence that the hyperphagic response to 8-OH-DPAT is mediated by 5-HT1A receptors. Eur J Pharmacol 150: 361–366

    Google Scholar 

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

    Google Scholar 

  • 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

    Google Scholar 

  • Middlemiss D (1987) Lack of effect of the putative 5-HT1A receptor agonist 8-OH-DPAT on 5-HT release in vitro. In: Dourish CT, Ahlenius S, Hutson PH (eds) Brain 5-HT1A receptors. Ellis Horwood, Chichester, pp 82–93

    Google Scholar 

  • Middlemiss DN (1984) 8-Hydroxy-2-(di-n-propylamino)tetralin is devoid of activity at the 5-hydroxytryptamine autoreceptor in rat brain. Implications for the proposed link between the autoreceptor and the [3H]5-HT recognition site. Naunyn-Schmiedebergs Arch Pharmacol 327: 18–22

    Google Scholar 

  • Middlemiss DN, Fozard JR (1983) 8-Hydroxy-2-(di-n-propylamino) tetralin discriminates between subtypes of the 5-HT1 recognition site. Eur J Pharmacol 90: 151–153

    Google Scholar 

  • Palacios JM, Pazos A, Hoyer D (1987) Characterization and mapping of 5-HT1A sites in the brain of animals and man. In: Dourish CT, Ahlenius S, Hutson PH (eds) Brain 5-HT1A receptors. Ellis Horwood, Chichester, pp 67–81

    Google Scholar 

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

    Google Scholar 

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

    Google Scholar 

  • Sinton CM, Fallon SL (1988) Electrophysiological evidence for a functional differentiation between subtypes of the 5-HT, receptor. Eur J Pharmacol 157: 173–181

    Google Scholar 

  • Sprouse JS, Aghajanian GK (1988) Responses of hippocampal pyramidal cells to putative serotonin 5-HT1A and 5-HT1B agonists: a comparative study with dorsal raphe neurons. Neuropharmacology 27: 707–715

    Google Scholar 

  • Steinbusch HWM (1981) Distribution of serotonin-immunoreactivity in the central nervous system of the rat—cell bodies and terminals. Neuroscience 6: 557–618

    Google Scholar 

  • Steinbusch HWM, Nieuwenhuys R (1983) The raphe nuclei of the rat brainstem: a cytoarchitectonic and immunohistochemical study. In: Emson PC (ed) Chemical neuroanatomy. Raven Press, New York, pp 131–207

    Google Scholar 

  • Taber Pierce E, Foote WE, Hobson JA (1976) The efferent connection of the nucleus raphe dorsalis. Brain Res 107: 137–144

    Google Scholar 

  • Törk I (1985) Raphe nuclei and serotonin containing systems. In: Paxinos G (ed) The rat nervous system. Academic Press, Sidney, pp 43–78

    Google Scholar 

Download references

Author information

Author notes

  1. V. Hillegaart

    Present address: Department of Psychology, University of Göteborg, Sweden

Authors and Affiliations

  1. Department of Psychology, University of Göteborg, Sweden

    S. Ahlenius

  2. Department of Zoology, University of Göteborg, Sweden

    V. Hillegaart

  3. Department of Pharmacology, University of Göteborg, Sweden

    S. Hjorth

  4. Department of Neuropharmacology, Astra Research Centre, SödertÄlje, Sweden

    S. Ahlenius

Authors
  1. V. Hillegaart
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. S. Hjorth
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. S. Ahlenius
    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

Hillegaart, V., Hjorth, S. & Ahlenius, S. 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 Transmission 81, 131–145 (1990). https://doi.org/10.1007/BF01245833

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF01245833

Keywords

Search

Navigation