Skip to main content
SpringerLink
Log in

Behavioural Correlates of the Activation of 5-HT Receptors

  • Chapter
Serotonin

Abstract

The precise role of neurones containing 5-hydroxytryptamine (5-HT) in behavioural control is unclear. A contributing factor to our lack of understanding has undoubtedly been the use of pharmacological tools devoid of selectivity for the three major populations of 5-HT receptor, 5-HT1like, 5-HT2 and 5-HT3 (and their subtypes), thought to exist in the CNS. A number of novel drugs with appreciable degrees of affinity and selectivity for these sites have recently become available and are proving to be useful tools for the re-examination of the functional roles of 5-HT. In this review of the behavioural pharmacology of 5-HT, attention is concentrated on some of the behavioural responses (largely in rodents) that have been proposed to reflect activation of specific 5-HT receptor subtypes. Unfortunately, little is known about some of the more complex behavioural paradigms that may help to predict the therapeutic potential of selectively manipulating 5-HT receptor subtypes in man.

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

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 74.99
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  • Arnt, J., Hyttel, J. and Larsen, J. J. (1984). The citalopram/5-HTP-induced head shake syndrome is correlated to 5-HT2 receptor affinity and also influenced by other transmitters. Acta Pharmacol. Toxicol., 55, 363–372

    Google Scholar 

  • Arriaga, F., Leitao, J., Mills, F. J., Padma, J., Ruiz, I., Tropa, J. and Sousa, M. P. (1984). R55667, an effective non-benzodiazepine anxiolytic. Proc. 14th CINP Congress, 726

    Google Scholar 

  • Bendotti, C. and Samanin, R. (1986). 8-Hydroxy-2-(di-n-propylamino)-tetralin (8-OH-DPAT) elicits eating in free-feeding rats by acting on central serotonin neurons. Eur. J. Pharmacol., 121, 147–150

    Google Scholar 

  • Bevan, P., Tulp, M. T. M. and Wouters, W. (1986). Are 5-HT1A binding sites relevant for the antihypertensive effects of DU 29373? Br. J. Pharmacol., 89, 637P

    Google Scholar 

  • Bockaert, J., Dumuis, A., Bouhelal, R., Sebben, M. and Cory, R. N. (1987). Piperazine derivatives including the putative anxiolytic drugs, buspirone and ipsapirone, are agonists at 5-HT1A receptors negatively coupled with adenylate cyclase in hippocampal neurons. Naunyn-Schmiedeberg’s Arch. Pharmacol., 335, 588–592

    Google Scholar 

  • Costall, B., Domeney, A. M., Naylor, R. J. and Tyers, M. B. (1987). Effects of the 5-HT3 receptor antagonist GR 38072F, on raised dopaminergic activity in the mesolimbic system of the rat and marmoset brain. Br. J. Pharmacol., 92, 881–894

    Google Scholar 

  • Cunningham, K. A., Callahan, P. M. and Appel, J. B. (1987). Discriminative stimulus properties of 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT): implications for understanding the actions of novel anxiolytics. Eur. J. Pharmacol., 138, 29–36

    Google Scholar 

  • Davis, M. (1980). Neurochemical modulation of sensory-motor reactivity: acoustic and tactile startle reflexes. Neurosci. Biobehav. Rev., 4, 241–263

    Google Scholar 

  • Davis, M., Cassella, J. V., Wrean, W. H. and Kehne, J. H. (1986). Serotonin receptor subtype agonists: Differential effects on sensorimotor reactivity measured with acoustic startle. Psychopharmacol. Bull., 22, 837–843

    Google Scholar 

  • Delorme, F., Froment, J. L. and Jouvet, M. (1966). Suppression du sommeil par la p-chloromethamphetamine et la pCPA. Comp. Rend. Soc. Biol., 160, 2347–2349

    Google Scholar 

  • Donohoe, T. P., Hutson, P. H. and Curzon, G. (1987). Blockade of dopamine receptors explains the lack of 5-HT stereotypy on treatment with the putative 5-HT1A agonist LY 165163. Psychopharmacology, 93, 82–86

    Google Scholar 

  • Dourish, C. T., Hutson, P. H. and Curzon, G. (1986a). Putative anxiolytics 8-OH-DPAT, buspirone and TVX Q 7821 are agonists at 5-HT1A autoreceptors in the raphe nuclei. Trends in Pharmacol. Sci., 7, 212–214

    Google Scholar 

  • Dourish, C. T., Hutson, P. H., Kennett, G. A. and Curzon, G. (1986b). 8-OH-DPAT-induced hyperphagia: the neural basis and possible therapeutic relevance. Appetite, 7, Suppl., 127–140

    Google Scholar 

  • Dourish, C. T., Clark, M. L., Fletcher, A. and Iversen, S. D. (1989). Evidence that blockade of 5-HT1 receptors elicits feeding in satiated rats. Psychopharmacology, 97, 54–58

    Google Scholar 

  • Dugovic, C. and Wauquier, A. (1987). 5-HT2 receptors could be primarily involved in the regulation of slow-wave sleep in the rat. Eur. J. Pharmacol., 137, 145–146

    Google Scholar 

  • Dzoljic, M. R., Saxena, P. R. and Ukponmwan, O. E. (1986). Activation of ‘5-HT1-like’ receptors stimulates wakefulness. Br. J. Pharmacol., 89, 522P

    Google Scholar 

  • Fozard, J. R. and Tricklebank, M. D. (1983). Differential effects of putative 5-HT1receptor agonists on responses to noxious stimuli. Naunyn-Schmiedeberg’s Arch. Pharmacol., 324, Suppl., R20

    Google Scholar 

  • Glennon, R. A., Young, R., Jacyno, J. M., Slusher, R. M. and Rosecrans, J. A. (1983). DOM-stimulus generalization to LSD and other hallucinogenic indoleal-kylamines. Eur. J. Pharmacol., 86, 453–459

    Google Scholar 

  • Gower, A. J. and Tricklebank, M. D. (1988). Alpha 2-adrenoceptor antagonist activity may account for the effects of buspirone in an anticonflict test in the rat. Eur. J. Pharmacol., 155, 129–137

    Google Scholar 

  • Hagan, R. M., Butler, A., Hill, J. M., Jordan, C. C., Ireland, S. J. and Tyers, M. B. (1987). Effect of the 5-HT3 receptor antagonist, GR 38032F, on responses to injection of a neurokinin agonist into the ventral tegmental area of the rat brain. Eur. J. Pharmacol., 138, 303–305

    Google Scholar 

  • Hibert, M., Mir, A. K., Maghioros, G., Moser, P., Middlemiss, D. N., Tricklebank, M. D. and Fozard, J. R. (1988). The pharmacological properties of MDL 73005EF: A potent and selective ligand at 5-HT1A receptors. Br. J. Pharmacol., 93, 2P

    Google Scholar 

  • Hjorth, S. and Carlsson, A. (1982). Buspirone: effects on central monoamine transmission — possible relevance to animal experimental and clinical findings. Eur. J. Pharmacol., 83, 299–303

    Google Scholar 

  • Hutson, P. H., Donohoe, T. P. and Curzon, G. (1987). Neurochemical and behavioural evidence for an agonist action of 1-[2-(4-aminophenyl)ethyl]-4-(3-trifluoromethylphenyl)piperazine (LY 165163) at central 5-HT receptors. Eur. J. Pharmacol., 138, 215–223

    Google Scholar 

  • Idzikowski, C., Mills, F. J. and Glennard, R. (1986). 5-Hydroxytryptamine-2 antagonist increases human slow wave sleep. Brain Res., 378, 164–168

    Google Scholar 

  • Iversen, S. D. (1984). 5-HT and anxiety. Neuropharmacology, 23, 1553–1560

    Google Scholar 

  • Jones, B. J., Oakley, N. R. and Tyers, M. D. (1987). The anxiolytic activity of GR 38032F, a 5-HT3 receptor antagonist, in the rat and Cynomolgus monkey. Br. J. Pharmacol., 90, 88P

    Google Scholar 

  • Kennett, G. A., Dourish, C. T. and Curzon, G. (1987). 5-HT1B agonists induce anorexia at a postsynaptic site. Eur. J. Pharmacol., 141, 429–435

    Google Scholar 

  • Lucki, I., Nobler, M. S. and Frazer, A. (1984). Differential actions of serotonin antagonists on two behavioural models of serotonin receptor activation in the rat. J. Pharmacol. Exp. Ther., 228, 133–139

    Google Scholar 

  • McKenney, J. D. and Glennon, R. A. (1986). TFMPP may produce its stimulus effects via a 5-HT1B mechanism. Pharmacol. Biochem. Behav., 24, 43–47

    Google Scholar 

  • Messing, R. B., Fisher, L. A., Phebus, L. and Lytle, L. D. (1976). Interaction of diet and drugs in the regulation of brain 5-hydroxyindoles and the response to painful electric shock. Life Sci., 18, 707–714

    Google Scholar 

  • Mir, A. K., Hibert, M., Tricklebank, M. D., Middlemiss, D. N., Kidd, E. J. and Fozard, J. R. (1988). MDL 72832: A potent, selective and stereospecific ligand with mixed agonist, antagonist properties at both central and peripheral 5-HT1Areceptors. Eur. J. Pharmacol., 149, 107–120

    Google Scholar 

  • Moser, P., Hibert, M., Middlemiss, D. N., Mir, A. K., Tricklebank, M. D. and Fozard J. R. (1988). Effects of MDL 73005EF in animal models predictive of anxiolytic activity. Br. J. Pharmacol., 93, 3P

    Google Scholar 

  • Peroutka, S. J. (1985). Selective interaction of novel anxiolytics with 5-hydroxytryptamine1A receptors. Biol. Psychiat., 20, 971–979

    Google Scholar 

  • Ransom, R. W., Asarch, K. B. and Shih, J. C. (1986). [3H]1-[2-(4-Aminophenyl)ethyl]-4-(3-trifluoromethylphenyl)piperazine: a selective radioli-gand for 5-HT1A receptors in rat brain. J. Neurochem., 46, 68–75

    Google Scholar 

  • Tricklebank, M. D., Forler, C. and Fozard, J. R. (1984). The involvement of subtypes of the 5-HT1 receptor and of catecholaminergic systems in the behavioural response to 8-hydroxy-2-(di-n-propylamino)tetralin in the rat. Eur. J. Pharmacol., 106, 271–282

    Google Scholar 

  • Tricklebank, M. D., Forler, C., Middlemiss, D. N. and Fozard, J. R. (1985). Subtypes of the 5-HT receptor mediating the behavioural responses to 5-methoxy-N,N-dimethyltryptamine in the rat. Eur. J. Pharmacol., 117, 15–24

    Google Scholar 

  • Tricklebank, M. D., Neill, J., Kidd, E. J. and Fozard, J. R. (1987). Mediation of the discriminative stimulus properties of 8-hydroxy-2-(di-n-propylamine)tetralin by the putative 5-HT1A receptor. Eur. J. Pharmacol., 133, 47–56

    Google Scholar 

  • Tyers, M. B., Costall, B., Domeney, A., Jones, B. J., Kelly, M. E., Naylor, R. J. and Oakley, N. R. (1987). The anxiolytic activities of 5HT3 antagonists in laboratory animals. Neurosci. Lett., Suppl. 29, S68.

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Neuroscience Research Centre, Merck Sharp and Dohme Research Laboratories, Terlings Park, Eastwick Road, Harlow, Essex, CM202QR, UK

    M. D. Tricklebank

Authors
  1. M. D. Tricklebank
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

  1. Department of Pharmacology, University of Sydney, Australia

    Ewan J. Mylecharane

  2. Baker Medical Research Institute, Prahran, Australia

    James A. Angus

  3. Department of Clinical and Experimental Pharmacology, University of Adelaide, Australia

    Ivan S. de la Lande

  4. Glaxo Group Research Ltd, Ware, England

    Patrick P. A. Humphrey

Copyright information

© 1989 The editors and contributors

About this chapter

Cite this chapter

Tricklebank, M.D. (1989). Behavioural Correlates of the Activation of 5-HT Receptors. In: Mylecharane, E.J., Angus, J.A., de la Lande, I.S., Humphrey, P.P.A. (eds) Serotonin. Satellite Symposia of the IUPHAR 10th International Congress of Pharmacology. Palgrave Macmillan, London. https://doi.org/10.1007/978-1-349-10114-6_11

Download citation

Publish with us

Policies and ethics

Search

Navigation