Skip to main content
SpringerLink
Log in

Anti-aversive role of serotonin in the dorsal periaqueductal grey matter

  • Original Investigations
  • Published:
Psychopharmacology Aims and scope Submit manuscript

Abstract

Microinjection of 5, 10, and 20 nmol serotonin (5-HT) and of 0.5, 1, and 2 nmol 5-methoxy-N, N-dimethyltryptamine (5-MeODMT) into the dorsal midbrain of rats bearing chronically implanted chemitrodes raised the electrical threshold for inducing escape behaviour following stimulation of the dorsal periaqueductal grey matter (DPAG). Linear regressions of log dose against drug-induced increase in aversive threshold were obtained for 5-HT and 5-MeODMT. The 5-MeODMT dose-effect curve was steeper and lay to the left of the 5-HT dose-effect curve. Local pre-treatment with 10 nmol metergoline or ketanserin blocked the anti-aversive effect of 10 nmol 5-HT, whereas pre-treatment with 100 nmol zimelidine potentiated this effect of 5-HT. The same dose of zimelidine raised the aversive threshold when given alone. These results suggest that 5-HT plays an inhibitory role in the DPAG controlling aversion, probably mediated by 5-HT2 receptors.

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

  • Berge OG, Chacho D, Hole K (1983) Inhibitory effect of 5-methoxy-N,N-dimethyltryptamine on the synaptosomal uptake of 5-hydroxytryptamine. Eur J Pharmacol 90:293–296

    Google Scholar 

  • Brandão ML, De Aguiar JC, Graeff FG (1982) GABA mediation of the anti-aversive action of minor tranqulizers. Pharmacol Biochem Behav 16:397–402

    Google Scholar 

  • Brownlee K (1965) Statistical theory and methodology: in science and engineering John Wiley, New York

    Google Scholar 

  • Cook L, Davidson AB (1973) Effects of behaviorally active drugs in a conflict-punishment procedure in rats. In: Garattini S, Mussini E, Randall LO (eds) The benzodiazepines. Raven Press, New York, p 327

    Google Scholar 

  • Cook L, Sepinwall J (1975) Reinforcement schedules and extrapolations to humans from animals in behavioral pharmacology. Fed Proc 34:1889–1897

    Google Scholar 

  • Evans L, Best J, Moore G, Cox J (1980) Zimelidine—a serotonin uptake blocker in the treatment of phobic anxiety. Prog Neuro-Psychopharmacol 4:75–80

    Google Scholar 

  • Fuxe K, Agnati L, Everitt B (1975) Effects of metergoline on central monoamine neurons. Evidence for a selective blockade of central 5-HT receptors. Neurosci Lett 1:283–291

    Google Scholar 

  • Fuxe K, Holmstedt B, Jonsson G (1972) Effects of 5-methoxy-N,N-dimethyltryptamine on central monoamine neurons. Eur J Pharmacol 19:25–34

    Google Scholar 

  • Geller I, Blum K (1970) The effects of 5-HTP on para-chlorophenylalanine (p-CPA) attenuation of “conflict” behavior. Eur J Pharmacol 9:319–324

    Google Scholar 

  • Geller I, Hartman RJ, Croy DJ (1974) Attenuation of conflict behavior with cinanserin, a serotonin antagonist: Reversal of the effect with 5-hydroxytryptophan and a-methyltryptamine. Res Commun Chem Pathol Pharmacol 7:165–174

    Google Scholar 

  • Graeff FG (1974) Tryptamine antagonists and punished behavior. J Pharmacol Exp Ther 189:344–350

    Google Scholar 

  • Graeff FG (1981) Minor tranquilizers and brain defense systems. Brazilian J Med Biol Res 14:239–265

    Google Scholar 

  • Graeff FG (1984) The anti-aversive action of minor tranquillizers. TIPS 5:230–233

    Google Scholar 

  • Graeff FG, Schoenfeld RI (1970) Tryptaminergic mechanisms in punished and nonpunished behavior. J Pharmacol Exp Pharmacol 173:277–283

    Google Scholar 

  • Iversen LL (1975) Uptake processes for biogenic amines. In: Iversen LL, Iversen SD, Snyder SH (eds) Handbook of psychopharmacology vol 3. Plenum, New York, p 381

    Google Scholar 

  • Kilts CD, Commissaris RL, Cordon JJ, Rech RH (1982) Lack of central 5-hydroxytryptamine influence on the anticonflict activity of diazepam. Psychopharmacology 78:156–164

    Google Scholar 

  • Kiser Jr RS, Lebovitz RM (1975) Monoaminergic mechanisms in aversive brain stimulation. Physiol Behav 15:47–56

    Google Scholar 

  • Kiser Jr RS, German DC, Lebovitz RM (1978) Serotonergic reduction of dorsal central gray area stimulation-produced aversion. Pharmacol Biochem Behav 9:27–31

    Google Scholar 

  • König JFR, Klippel RA (1963) The rat brain in stereotaxic coordinates. William and Wilkins. Baltimore

    Google Scholar 

  • Leone CML, De Aguiar JC, Graeff FG (1983) Role of 5-hydroxytryptamine in amphetamine effects on punished and unpunished behaviour. Psychopharmacology 80:78–82

    Google Scholar 

  • Leroux AG, Myers RD (1975a) New multi-purpose chemitrodes for electrical and chemical stimulation of localized perfusion of the brain. Pharmacol Biochem Behav 3:311–315

    Google Scholar 

  • Leroux AG, Myers RD (1975b) Action of serotonin microinjected into hypothalamic sites at which electrical stimulation produced aversive responses in the rat. Physiol Behav 14:501–505

    Google Scholar 

  • Leysen JE, Awouters F, Kennis L, Laduron PM, Vanderberk J, Janssen PAJ (1981) Receptor binding profile of R41468, a novel antagonist at 5-HT2 receptors. Life Sci 28:1015–1022

    Google Scholar 

  • Marseillan RF (1977) A solid state sine-wave stimulator. Physiol Behav 19:339–340

    Google Scholar 

  • Montastruc JL, Tran MA, Charlet JP, Gaillard-Plaza G, David J, Cotonat J, Guiraud B, Rascol A (1983) Etude des propriétés analgésiques et des concentrations plasmatiques de clomipramine dans les douleurs chroniques. Rev Neurol (Paris) 139:583–587

    Google Scholar 

  • Morato de Carvalho S, De Aguiar JC, Graeff FG (1981) Effect of minor tranquilizers, tryptamine antagonists and amphetamine on behavior punished by brain stimulation. Pharmacol Biochem Behav 15:351–356

    Google Scholar 

  • Olds J, Olds ME (1965) Drives, rewards and the brain. In: Barron F, Dement WC (eds) New directions in psychology, vol. 2. Holt, Rinehart and Winston, New York, p 329

    Google Scholar 

  • Peroutka SJ, Lebovitz RM, Snyder SH (1981) Two distinct central serotonin receptors with different physiological functions. Science 212:827–829

    Google Scholar 

  • Petersen EN, Lassen JB (1981) A water lick conflict paradigm using drug experienced rats. Psychopharmacology 75:236–239

    Google Scholar 

  • Robichaud RC, Sledge KL (1969) The effects of p-chlorophenylalanine on experimentally induced conflict in the rat. Life Sci 8:965–969

    Google Scholar 

  • Ross SB, Ögren SO, Renyi A (1976) (Z)-Dimethylamino-1-(4-bromophenyl)-1-(3-pyridyl) propene (H102/09), a new selective inhibitor of the neuronal 5-hydroxytryptamine uptake. Acta Pharmacol (Kbh) 39:152–166

    Google Scholar 

  • Schenberg LC, Graeff FG (1978) Role of the periaqueductal gray substance in the antianxiety action of benzodiazepines. Pharmacol Biochem Behav 9:287–295

    Google Scholar 

  • Schoenfeld RI (1976) Lysergic acid diethylamide-and mescaline-induced attenuation of the effect of punishment in the rat. Science 192:801–803

    Google Scholar 

  • Shephard RA, Buxton DA, Broadhurst PL (1982) Drug interactions do not support reduction in serotonin turnover as the mechanism of action of benzodiazepines. Neuropharmacology 21:1027–1032

    Google Scholar 

  • Slater P, Patel S (1983) Autoradiographic distribution of serotonin2 receptors in rat brain. Eur J Pharmacol 92:297–298

    Google Scholar 

  • Stein L, Wise CD, Berger BD (1973) Antianxiety action of benzodiazepines. Decrease in activity of serotonin neurons in the punishment system. In: Garattini S, Mussini E, Randall LO (eds) The benzodiazepines. Raven Press, New York, p 299

    Google Scholar 

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

    Google Scholar 

  • Thiébot M-H, Soubrié P, Hamon M, Simon P (1984) Evidence against the involvement of serotonergic neurons in the anti-punishment activity of diazepam in the rat. Psychopharmacology 82:355–359

    Google Scholar 

  • Tye NC, Everitt BJ, Iversen SD (1977) 5-hydroxytryptamine and punishment. Nature 268:741–742

    Google Scholar 

  • Van Nueten JM, Janssen PAJ, Van Beek J, Xhonneux R, Verbeuren TJ, Vanhoutte PM (1981) Vascular effects of ketanserin (R41468), a novel antagonist of 5-HT2 serotonergic receptors. J Pharmacol Exp Ther 218:217–230

    Google Scholar 

  • Wise CD, Berger BD, Stein L (1972) Benzodiazepines: Anxiety-reducing activity by reduction of serotonin turnover in the brain. Science 177:180–183

    Google Scholar 

  • Wise CD, Berger BD, Stein L (1973) Evidence of a-noradrenergic reward receptors and serotonergic punishment receptors in the rat brain. Biol Psychiatr 6:3–21

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Pharmacology, Faculty of Medicine, USP, BR 14100, Ribeirão Preto, SP, Brazil

    M. T. B. Schütz, J. C. de Aguiar & F. G. Graeff

Authors
  1. M. T. B. Schütz
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. J. C. de Aguiar
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. F. G. Graeff
    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

Schütz, M.T.B., de Aguiar, J.C. & Graeff, F.G. Anti-aversive role of serotonin in the dorsal periaqueductal grey matter. Psychopharmacology 85, 340–345 (1985). https://doi.org/10.1007/BF00428199

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF00428199

Key words

Search

Navigation