Skip to main content
SpringerLink
Log in

A pharmacological analysis of the eating response induced by 8-OH-DPAT injected into the dorsal raphé nucleus reveals the involvement of a dopaminergic mechanism

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

Abstract

Direct injection of the 5-hydroxytryptamine (5-HT) agonist 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) into the dorsal raphé nucleus (DRN) dose dependently increased food intake in free feeding rats. The hypothesis that this effect is mediated by 5-HT1A receptors was tested by investigating the abilities of the putative 5-HT1A antagonists metergoline, propanolol and spiperone to prevent 8-OH-DPAT-induced eating. Metergoline failed to affect 8-OH-DPAT-induced eating when injected either peripherally or into the DRN. Peripherally injected propranolol and spiperone prevented 8-OH-DPAT-induced eating, but these drugs were ineffective when injected into the DRN. These results indicate that 8-OH-DPAT-induced eating may not involve 5-HT1A receptors within the DRN. The ability of peripherally injected spiperone to prevent the eating response to 8-OH-DPAT reflects its dopamine blocking activity since haloperidol was an effective antagonist of 8-OH-DPAT-eating. This result may indicate that 8-OH-DPAT produces a general behavioural activation by reducing the inhibitory influence which 5-HT normally exerts over the nigrostriatal dopamine pathway, and that this behavioural activation is expressed as eating when food is the most salient goal object present.

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

  • Aghajanian GK, Sprouse JS, Rasmussen U (1987) Physiology of the Midbrain Serotonin System. In: Meltzer HY (ed) Psychopharmacology: the third generation of progress. Raven Press, New York, pp 141–149

    Google Scholar 

  • Antelman SM, Szechtman H (1975) Tail pinch induces eating in sated rats which appears to depend on nigrostriatal dopamine. Science 189:731–733

    PubMed  Google Scholar 

  • Azami J, Llewelyn MB, Roberts MHT (1980) An extra-fine assembly for intracerebral microinjection. J Physiol (Lond) 305:18–19

    Google Scholar 

  • Azmitia EC (1978) The serotonin-producing neurons of the midbrain median and dorsal raphé nuclei. In: Iversen LL, Iversen SD, Snyder SH (eds) Handbook of psychopharmacology, vol 9. Plenum Publishing, New York, pp 233–314

    Google Scholar 

  • Bendotti C, 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

    Article  PubMed  Google Scholar 

  • Blundell JE (1984) Serotonin and appetite. Neuropharmacology 23:1537–1551

    Article  PubMed  Google Scholar 

  • Cervo L, Grignaschi G, Samanin R (1988) 8-Hydroxy-2-(di-n-propylamino)tetralin, a selective serotonin1A receptor agonist, reduces the immobility of rats in the forced swimming test by acting on the nucleus raphé dorsalis. Eur J Pharmacol 158:53–59

    Article  PubMed  Google Scholar 

  • De Montigny C, Blier P, Chaput Y (1984) Electrophysiologically identified serotonin receptors in the rat CNS. Neuropharmacology 23:1511–1520

    Article  PubMed  Google Scholar 

  • Dourish CT (1987) Brain 5-HT1A receptors and anxiety. In: Dourish CT, Ahlenius S, Hutson PH (eds) Brain 5-HT1A receptors, behavioural and neurochemical pharmacology. Ellis Horwood, Chichester, London, pp 261–277

    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

    Article  PubMed  Google Scholar 

  • Dourish CT, Cooper SJ, Gilbert F, Coughlan J, Iversen SD (1988) The 5-HT1A agonist 8-OH-DPAT increases consumption of palatable wet mash and liquid diets in the rat. Psychopharmacology 94:58–63

    Article  PubMed  Google Scholar 

  • Dray A, Davies J, Oakley NR, Tongroach P, Vellucci S (1978) The dorsal and medial raphé projections to the substantia nigra in the rat. Electrophysiological biochemical and behavioural observations. Brain Res 151:431–442

    Article  PubMed  Google Scholar 

  • Fletcher PJ (1987) 8-OH-DPAT elicits gnawing and eating of solid but not liquid foods. Psychopharmacology 92:192–196

    Article  PubMed  Google Scholar 

  • Fletcher PJ (1988) Increased food intake in satiated rats induced by the 5-HT antagonists methysergide, metergoline and ritanserin. Psychopharmacology 96:237–242

    Article  PubMed  Google Scholar 

  • Fozard JR, Mir AK, Middlemiss DN (1987) Cardiovascular response to 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) in the rat: site of action and pharmacological analysis. J Cardiovasc Pharmacol 9:328–347

    PubMed  Google Scholar 

  • Gilman AG, Goodman LS, Rall TW, Murad F (1985) Goodman and Gilman's The pharmacological basis of therapeutics (7th Edition) MacMillan Publishing Co, New York

    Google Scholar 

  • Goldman CK, Marino L, Leibowitz SF (1985) Postsynapticα 2-noradrenergic receptors mediate feeding induced by paraventricular nucleus injection of norepinephrine and clonidine. Eur J Pharmacol 115:11–19

    Article  PubMed  Google Scholar 

  • Graeff FG, Brandao ML, Audi EA, Schutz MTB (1986) Modulation of the brain aversive system by gabaergic and serotonergic mechanisms. Behav Brain Res 21:65–72

    Article  PubMed  Google Scholar 

  • Gudelsky GA, Koenig JI, Meltzer HY (1986) Thermoregulatory responses to serotonin (5-HT) receptor stimulation in the rat: evidence for opposing roles of 5-HT2 and 5-HT1A receptors. Neuropharmacology 25:1307–1313

    Article  PubMed  Google Scholar 

  • Hall MD, El-Mestikawy S, Emerit MB, Pichat L, Hamon M, Gozlan H (1985) [3H]8-Hydroxy-2-(di-n-propylamino)tetralin binding to pre- and postsynaptic 5-hydroxytryptamine sites in various regions of the rat brain. J Neurochem 44:1685–1696

    PubMed  Google Scholar 

  • Hjorth S, Carlsson A, Magnusson T, Arvidsson L-E (1987) In vivo biochemical characterization of 8-OH-DPAT: evidence for 5-HT receptor selectivity and agonist action in the rat CNS. In: Dourish CT, Ahlenius S, Hutson PH (eds) Brain 5-HT1A receptors, behavioural and neurochemical pharmacology. Ellis Horwood, Chichester, London, pp 94–105

    Google Scholar 

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

    PubMed  Google Scholar 

  • Hutson PH, Dourish CT, Curzon G (1986) Neurochemical and behavioural evidence for mediation of the hyperphagic action of 8-OH-DPAT by 5-HT cell body autoreceptors. Eur J Pharmacol 129:347–352

    Article  PubMed  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

    Article  PubMed  Google Scholar 

  • Kelley AE, Gauthier AM, Lang CG (1989) Amphetamine microinjections into distinct striatal subregions cause dissociable effects on motor and ingestive behaviour. Behav Brain Res (in press)

  • Kennett GA, Dourish CT, Curzon G (1987) Antidepressant-like action of 5-HT1A agonists and conventional antidepressants in an animal model of depression. Eur J Pharmacol 134:265–274

    Article  PubMed  Google Scholar 

  • Lum JT, Piercey MF (1988) Electrophysiological evidence that spiperone is an antagonsit of 5-HT1A receptors in the dorsal raphé nucleus. Eur J Pharmacol 149:9–15

    Article  PubMed  Google Scholar 

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

    Article  PubMed  Google Scholar 

  • Mogenson GJ (1982) Studies of the nucleus accumbens and its mesolimbic dopaminergic afferents in relation to ingestive behavior and reward. In: Hoebel BG, Novin D (eds) The neural basis of feeding and reward. Haer Institute, pp 275–287

  • Montgomery AMJ, Willner P, Muscat R (1988a) Evidence for dopaminergic mediation of 8-OH-DPAT hyperphagia. Psychopharmacology 96:(Suppl.) S 39

    Google Scholar 

  • Montgomery AMJ, Willner P, Muscat R (1988b) Behavioural specificity of 8-OH-DPAT-induced feeding. Psychopharmacology 94:110–114

    Article  PubMed  Google Scholar 

  • Paxinos G, Watson C (1986) The rat brain in stereotaxic coordinates, 2nd Edition. Academic Press, New York

    Google Scholar 

  • Pijnenburg AJJ, Honig WMM, Van Rossum JM (1975) Effects of antagonists upon locomotor stimulation induced by injection of dopamine and noradrenaline into the nucleus accumbens of nialamide-pretreated rats. Psychopharmacology 41:175–180

    Article  Google Scholar 

  • Robbins TW, Everitt BJ (1982) Functional studies of the central catecholamines. Int Rev Neurobiol 23:303–365

    PubMed  Google Scholar 

  • Sleight AJ, Smith RJ, Marsden CA, Palfreyman MG (1988) Is the hyperphagic response to 8-OH-DPAT a model for 5-HT1A receptor responsiveness? Br J Pharmacol 96:875P

  • Spano PF, Biggio G, Casu M, Gessa GL, Bareggi SR, Govoni S, Trabucchi M (1978) Interaction of metergoline with striatal dopamine system. Life Sci 23:2383–2392

    Article  PubMed  Google Scholar 

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

    Article  PubMed  Google Scholar 

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

    Article  PubMed  Google Scholar 

  • Tricklebank MD, Forler C, Fozard JR (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

    Article  PubMed  Google Scholar 

  • Ugedo L, Grenhoff J, Svensson TM (1989) Ritanserin, a 5-HT2 receptor antagonist, activates midbrain dopamine neurons by blocking serotonergic inhibition. Psychopharmacology 98:45–50

    Article  PubMed  Google Scholar 

  • Verge D, Daval G, Patey A, Gozlan M, El Mestikaway S, 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

    Article  PubMed  Google Scholar 

  • White NM (1986) Control of sensorimotor function by dopaminergic nigrostriatal neurons: influence on eating and drinking. Neurosci Biobehav Rev 10:15–36

    Article  PubMed  Google Scholar 

  • Winn P, Williams SF, Herberg LJ (1982) Feeding stimulated by very low doses ofd-amphetamine administered systemically or by microinjection into the striatum. Psychopharmacology 78:336–341

    Article  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Neuropsychiatric Research Unit, Medical Research Building, University of Saskatchewan, S7N OWO, Saskatoon, Saskatchewan, Canada

    Paul J. Fletcher & Michael Davies

Authors
  1. Paul J. Fletcher
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Michael Davies
    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

Fletcher, P.J., Davies, M. A pharmacological analysis of the eating response induced by 8-OH-DPAT injected into the dorsal raphé nucleus reveals the involvement of a dopaminergic mechanism. Psychopharmacology 100, 188–194 (1990). https://doi.org/10.1007/BF02244404

Download citation

  • Received:

  • Revised:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF02244404

Key words

Search

Navigation