Skip to main content
SpringerLink
Log in

Effect of dopamine D-1 and D-2 receptor selective drugs on dopamine release and metabolism in rat striatum in vivo

  • Published:
Naunyn-Schmiedeberg's Archives of Pharmacology Aims and scope Submit manuscript

Summary

The effect of the dopamine (DA) D-1 agonist SKF 38393, the D-2 agonist LY 171555 and the mixed D-1/D-2 agonist apomorphine on striatal DA release and metabolism was tested in vivo using an intracerebral dialysis method in halothane-anaesthetized rats. The specificity of responses to these agonists was tested using the selective DA antagonists SCH 23390 (D-1) and sulpiride (D-2).

Both LY 171555, 0.01 mg/kg, and SKF 38393, 10 mg/kg, reduced levels of DA in striatal perfusates. Neither SCH 23390, 0.5 and 5 mg/kg, nor sulpiride, 10 mg/kg, affected levels of DA in striatal perfusates, but 250 mg/kg sulpiride caused a DA increase. The decrease of DA levels induced by LY 171555 (0.01 mg/kg) was prevented by pretreatment with sulpiride (10 mg/kg) but not SCH 23390 (0.5 mg/kg). In comparison, pretreatment with SCH 23390 (0.5 mg/kg) completely inhibited the reduction of DA induced by SKF 38393 (10 mg/kg) while sulpiride (10 mg/kg) was without effect. Apomorphine (0.05 mg/kg) also decreased DA in striatal perfusates and this action was partially inhibited by both SCH 23390 (0.5 mg/kg) and sulpiride (10 mg/kg).

Levels of the DA metabolite DOPAC in striatal perfusates also significantly decreased following LY 171555 (0.01 mg/kg) and apomorphine (0.05 mg/kg) but not SKF 38393 (10 mg/kg). The antagonist SCH 23390, in a dose, 0.5 mg/kg, that alone did not increase levels of DOPAC, inhibited the reduction of DOPAC induced by both LY 171555 and apomorphine. Sulpiride, 10 mg/kg, caused a marked increase in striatal DOPAC and this was not affected by a subsequent injection of LY 171555, SKF 38393 or apomorphine.

We conclude from these data that DA release in rat striatum is autoregulated by independent D-1 and D-2 receptor-linked mechanisms. In contrast, the level of DA metabolism is controlled by a D-2 receptor-coupled mechanism which can be influenced by the D-1 receptor. This study provides further evidence that DA release and DA synthesis/metabolism are able to change independent of each other.

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, Bunney BS (1973) Central dopaminergic neurons: Neurophysiological identification and responses to drugs. In: Usdin E, Snyder SH (eds) Frontiers in catecholamine research. Pergamon Press, New York, pp 643–663

    Google Scholar 

  • Brown F, Cambell W, Mitchell PJ, Randall K (1985) Dopamine autoreceptors and the effects of drugs on locomotion and dopamine synthesis. Br J Pharmacol 84:853–860

    Google Scholar 

  • Anden NE (1972) Dopamine turnover in the corpus striatum and the limbic system after treatment with neuroleptic and antiacetylcholine drugs. J Pharm Pharmacol 24:905–906

    Google Scholar 

  • Arbilla S, Langer SZ (1981) Stereoselectivity of presynaptic autoreceptors modulating DA release. Eur J Pharmacol 76:345–351

    Google Scholar 

  • Arnt J, Hyttel J (1984) Differential inhibition by dopamine D1 and D2 antagonists of circling behaviour induced by dopamine agonists in rats with unilateral 6-hydroxydopamine lesions. Eur J Pharmacol 102:349–354

    Google Scholar 

  • Boyce S, Kelly E, Davis A, Fleminger S, Jenner P, Marsden CD (1985) SCH 23390 may alter dopamine-mediated motor behaviour via striatal D1 receptors. Biochem Pharmacol 34:1665–1669

    Google Scholar 

  • Bradbury AJ, Cannon JG, Costall B, Naylor RJ (1984) A comparison of dopamine agonist action to inhibit locomotor activity and to induce sterotyped behaviour in the mouse. Eur J Pharmacol 105:33–47

    Google Scholar 

  • Bunney BS, Walters JR, Roth RH, Aghajanian GK (1973) Dopaminergic neurons: Effect of antipsychotic drugs and amphetamine on single cell activity. J Pharmacol Exp Ther 185:560–572

    Google Scholar 

  • Carlsson A, Lindqvist M (1963) Effect of chlorpromazine or haloperidol on formation of 3-methoxytyramine and normetanephrine in mouse brain. Acta Pharmacol Toxicol 20:140–144

    Google Scholar 

  • DiChiara G, Porceddu ML, Vargiu L, Argiolas A, Gessa GL (1976) Evidence for dopamine receptors mediating sedation in the mouse brain. Nature 264:564–567

    Google Scholar 

  • Farnebo LO, Hamberger B (1971) Drug induced changes in the release of 3H-monoamines from field stimulated rat brain slices. Acta Physiol Scand 371:35–44

    Google Scholar 

  • Fletcher GH, Starr MS (1985) SKF 38393 and apomorphine modify locomotion and exploration in rats placed on a holeboard by separate actions at dopamine D1 and D2 receptors. Eur J Pharmacol 117:381–385

    Google Scholar 

  • Fuller RW, Hemrick-Luecke SK (1984) Decrease in hypothalamic epinephrine concentration and other neurochemical changes produced by quinpirole, a dopamine agonist, in rats. J Neural Trans 61:161–173

    Google Scholar 

  • Gessa GL, Porceddu ML, Collu M, Mereu G, Serra M, Ongini E, Biggio G (1985) Sedation and sleep induced by high doses of apomorphine after blockade of D1 receptors by SCH 23390. Eur J Pharmacol 109:269–274

    Google Scholar 

  • Groves PM, Fenster GA, Tepper JM, Nakamura S, Young SJ (1981) Changes in dopaminergic terminal excitability induced by amphetamine and haloperidol. Brain Res 221:425–431

    Google Scholar 

  • Herrera-Marschitz M, Ungerstedt U (1984a) Evidence that apomorphine and pergolide-induce contralateral rotation in rats by different actions on D1 or D2 receptor sites. Eur J Pharmacol 98:165–176

    Google Scholar 

  • Herrera-Marschitz M, Ungerstedt U (1984b) Evidence that striatal efferents relate to different dopamine receptors. Brain Res 323:269–278

    Google Scholar 

  • Hyttel J (1984) Functional evidence for selective dopamine D1 receptor blockade by SCH 23390. Neuropharmacology 23:1395–1401

    Google Scholar 

  • Imperato A, DiChiara G (1984) Trans-striatal dialysis coupled to reverse phase high performance liquid chromatography with electrochemical detection. A new method for the study of the in vivo release of endogenous dopamine and metabolites. J Neuroscience 4:966–977

    Google Scholar 

  • Imperato A, DiChiara G (1985) Dopamine release and metabolism in awake rats after systemic neuroleptics as studied by trans-striatal dialysis. J Neuroscience 5:297–306

    Google Scholar 

  • Iorio LC, Barnett A, Leitz FH, Houser VP, Korduba CA (1983) SCH 23390, a potential benzazapine antipsychotic with unique interactions on dopaminergic systems. J Pharmacol Exp Ther 226:462–468

    Google Scholar 

  • Jenner P, Marsden CD (1979) The substituted benzamides—A novel class dopamine antagonists. Life Sci 25:479–486

    Google Scholar 

  • Kebabian J, Calne DB (1979) Multiple receptors for dopamine. Nature 277:93–96

    Google Scholar 

  • Kebabian J, Agui T, van Oene JC, Shigematsu K, Saavedra JM (1986) The D1 receptor: new perspectives. Trends Neurosc 7:96–99

    Google Scholar 

  • Kehr W, Carlsson A, Lindqvist M, Magnusson T, Atack CV (1972) Evidence for a receptor mediated control of striatal tyrosine hydroxylase activity. J Pharm Pharmacol 24:744–747

    Google Scholar 

  • Lehman J, Briley M, Langer SZ (1983) Characterization of dopamine autoreceptors and 3H spiperone binding sites in vitro with classical and novel dopamine receptor agonists. Eur J Pharmacol 88:11–26

    Google Scholar 

  • Ljungberg T, Ungerstedt U (1976) Automatic registration of behaviour related to dopamine and noradrenaline transmission. Eur J Pharmacol 36:181–187

    Google Scholar 

  • Mereu G, Casu M, Gessa GL (1983) (−)-Sulpiride activates the firing rate and tyrosine hydroxylase activity of dopaminergic neurons in unanaesthetized rats. Brain Res 264:105–110

    Google Scholar 

  • Molloy AG, Waddington JL (1985) The enantiomers of SKF 83566, a new selective D-1 dopamine antagonist, stereospecifically block stereotyped behaviour induced by apomorphine and by the selective D-2 agonist RU 24213. Eur J Pharmacol 116:183–186

    Google Scholar 

  • Niemegeers CJE, Janssen PAJ (1979) A systemic study of the pharmacological activities of dopamine antagonists. Life Sci 24:2201–2216

    Google Scholar 

  • Onali P, Mereu G, Olianas MC, Bunse B, Rossetti Z, Gessa GL (1985) SCH 23390, a selective D1 dopamine receptor blocker, enhances the firing rate of nigral dopaminergic neurons but fails to activate striatal tyrosine hydroxylase. Brain Res 340:1–7

    Google Scholar 

  • Ouimet CC, Miller PE, Hemmings HC, Walaas SI, Greengard P (1984) DARPP-32, a dopamine- and adenosine 3,5-monophosphate-regulated phosphoprotein enriched in dopamine- innervated brain regions. S Neuroscience 4:111–124

    Google Scholar 

  • Pellegrino LJ, Cushman AJ (1967) A sterotaxic atlas of the rat brain. Appleton Century Crofts, New York

    Google Scholar 

  • Plantje JF, Daus FJ, Hansen HA, Stoof JC (1964) SCH 23390 blocks D1 and D2 dopamine receptors in rat neostriatum in vitro. Naunyn-Schmiedeberg's Arch Pharmacol 327:180–182

    Google Scholar 

  • Pugh MT, O'Boyle KM, Molloy AG, Waddington JL (1985) Effects of the putative D-1 antagonist SCH 23390 on stereotyped behaviour induced by the D-2 agonist RU 24213. Psychopharmacology 87:308–312

    Google Scholar 

  • Reiman W, Zumstein A, Jackisch R, Starke K, Hertting G (1979) Effect of extracellular dopamine on the release of dopamine in the rabbit caudate nucleus: Evidence for a dopaminergic feedback inhibition. Naunyn-Schmiedeberg's Arch Pharmacol 306:53–60

    Google Scholar 

  • Saller CF, Salama AI (1985) Dopamine receptor subtypes: in vivo biochemical evidence for functional interaction. Eur J Pharmacol 109:297–300

    Google Scholar 

  • Seeman P (1980) Brain dopamine receptors. Pharmacol Reviews 32:229–313

    Google Scholar 

  • Setler PE, Sarau HM, Zirkle CL, Saunders HL (1978) The central effects of a novel dopamine agonist. Eur J Pharmacol 50:419–430

    Google Scholar 

  • Sharp T, Zetterström T, Ungerstedt U (1986) An in vivo study of dopamine release and metabolism in rat brain regions using intracerebral dialysis. J Neurochem 47:113–122

    Google Scholar 

  • Starke K, Späth L, Lang JD, Adelung C (1983) Further functional in vitro comparison of pre- and postsynaptic dopamine receptors in the rabbit caudate nucleus. Naunyn-Schmiedeberg's Arch Pharmacol 323:298–306

    Google Scholar 

  • Stoof JC, Kebabian J (1984) Two dopamine receptors: Biochemistry physiology and pharmacology. Life Sci 35:2281–2296

    Google Scholar 

  • Strömbom U (1976) Catecholamine receptor agonists: Effects on motor activity and rate of tyrosine hydroxylation in mouse brain. Naunyn-Schmiedeberg's Arch Pharmacol 297:167–176

    Google Scholar 

  • Ståhle L, Ungerstedt U (1986) Effects of neuroleptic drugs on the inhibition of exploratory behaviour induced by a low dose of apomorphine. Implication for the identity of dopamine receptors. Pharmacol Biochem Behav (in press)

  • Trabucchi MR, Longoni P, Fresia P, Spano PF (1975) Sulpiride: a study of the effects on dopamine receptors in rat striatum and limbic forebrain. Life Sci 17:1551–1556

    Google Scholar 

  • Tsuruta K, Frey EA, Grewe CW, Cote TE, Eskay RL, Kebabian JW (1981) Evidence that LY-141865 specifically stimulates the D2 dopamine receptor. Nature 292:463–465

    Google Scholar 

  • Ungerstedt U (1971) Postsynaptic super-sensitivity after 6-hydroxydopamine induced degeneration of the nigro-striatal dopamine system. Acta Physiol Scand (suppl) 367:69–93

    Google Scholar 

  • Ungerstedt U (1984) Measurement of neurotransmitter release by intracranial dialysis. In: Marsden CA (ed) Measurement of neurotransmitter release in vivo. J Wiley & Sons, New York, pp 81–105

    Google Scholar 

  • Ungerstedt U, Herrera-Marschitz M, Jungnelius U, Ståhle L, Tossman U, Zetterström T (1982) Dopamine synaptic mechanisms reflected in studies combining behavioural recordings and brain dialysis. In: Kohsaka M (ed) Advances in dopamine research, Advances in the biosciences. Pergamon Press, Oxford New York, pp 219–231

    Google Scholar 

  • Walters JR, Bergström DA, Bromley SD, Waszczak BL, Jackson (1983) Neurophysiological effect of dopamine agonists in the substantia nigra and globus pallidus. In: Carlsson A, Nilsson JLG (eds) Dopamine receptor agonists. Acta Pharm Suecica Suppl 1:186–199

  • Westerink BHC, Korf J (1976) Comparison of the effect of drugs on dopamine metabolism in the substantia nigra and the corpus striatum of the rat brain. Eur J Pharmacol 40:131–136

    Google Scholar 

  • Westerink BHC (1979) The effect of drugs on dopamine biosynthesis and metabolism in the brain. In: Horn AS, Korf J, Westerink BHC (eds) The neurobiology of dopamine. Academic Press, London New York San Francisco, pp 255–291

    Google Scholar 

  • Zetterström T, Ungerstedt U (1984) Effect of apomorphine on the in vivo release of dopamine and its metabolites studied by intracerebral dialysis. Eur J Pharmacol 97:29–36

    Google Scholar 

  • Zetterström T, Sharp T, Marsden CA, Ungerstedt U (1983) In vivo measurement of dopamine and its metabolites by intracerebral dialysis: Changes after d-amphetamine. J Neurochem 41:1769–1773

    Google Scholar 

  • Zetterström T, Sharp T, Ungerstedt U (1984) Effect of neuroleptic drugs on striatal dopamine release and metabolism in the awake rat studied by intracerebral dialysis. Eur J Pharmacol 106:27–37

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Pharmacology, Karolinska Institutet, S-104 01, Stockholm, Sweden

    T. Zetterström, T. Sharp & U. Ungerstedt

Authors
  1. T. Zetterström
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. T. Sharp
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. U. Ungerstedt
    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

Zetterström, T., Sharp, T. & Ungerstedt, U. Effect of dopamine D-1 and D-2 receptor selective drugs on dopamine release and metabolism in rat striatum in vivo. Naunyn-Schmiedeberg's Arch. Pharmacol. 334, 117–124 (1986). https://doi.org/10.1007/BF00505810

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF00505810

Key words

Search

Navigation