Skip to main content
Log in

Involvement of cholecystokinin receptors in the control of striatal dopamine autoreceptors

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

Summary

The interaction of locally perfused cholecystokinin-8 (sulphated) with systemically administered apomorphine was studied on the release of dopamine and its metabolites using microdialysis in the neostriatum of the halothane-anaesthetized male rat. Dialysate levels of dopamine, 3,4-dihydroxyphenylacetic acid and homovanillic acid were assayed by high performance liquid chromatography in combination with electrochemical detection. Perfusion with cholecystokinin-8 (100 μM but not 1 μM or 10 nM) increased the dialysate levels of dopamine without affecting those of DOPAC or HVA. At low concentrations (1 μM and 10 nM but not 1 nM), cholecystokinin-8 counteracted the inhibitory effect of apomorphine (0.05 mg/kg, s. c.) on dopamine release. This counteraction was antagonized by perfusion with the cholecystokinin-8 antagonist proglumide (3 μM). At this concentration, proglumide perfused alone was without effect on basal or apomorphine-reduced levels of dopamine. The results indicate a facilitatory effect of cholecystokinin-8 on dopamine release in rat neostriatum only at high concentrations. At lower concentrations, cholecystokinin-8 appears to modulate dopamine release by an inhibitory effect on dopamine autoreceptors possibly involving an intramembrane interaction between presynaptic cholecystokinin-8 receptors and dopamine autoreceptors.

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

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

  • Agnati LF, Fuxe K (1983) Subcortical limbic 3H-N-propylnorapomorphine binding sites are markedly modulated by cholecystokinin-8 in vitro. Biosci Rep 3:1101–1105

    Google Scholar 

  • Agnati LF, Celani MF, Fuxe K (1983) Cholecystokinin peptides in vitro modulate the characteristics of striatal [3H]N-propylnorapomorphine binding sites. Acta Physiol Scand 118:79–81

    Google Scholar 

  • Bean AJ, During MJ, Roth RH (1989) Stimulation-induced release of coexistent transmitters in the prefrontal cortex: an in vivo microdialysis study of dopamine and neurotensin release. J Neurochem 53:655–657

    Google Scholar 

  • Bunney BS, Chiodo LA, Freeman AS (1985) Further studies on the specificity of proglumide as a selective cholecystokinin antagonist in the central nervous system. Ann NY Acad Sci USA 448:345–351

    Google Scholar 

  • Carlson A (1975) Receptor mediated control of dopamine metabolism. In: Usdin E, Bunney WE (eds) Catecholamines: Basic and Clinical Frontiers. Dekker, New York, pp 49–65

    Google Scholar 

  • Chiodo LA, Bunney BS (1983) Proglumide: selective antagonism of excitatory effects of cholecystokinin in the central nervous system. Science 219:1449–1451

    Google Scholar 

  • Commisong JW (1985) Monoamine metabolites; their relationship and lack of relationship to monoamine neuronal activity. Biochem Pharmacol 34:1127–1131

    Google Scholar 

  • Di Chiara G, Proceddu ML, Vargin L, Stefanini E, Gessa GL (1976) Evidence for dopamine receptors mediating sedation in the mouse. Nature 264:564–567

    Google Scholar 

  • von Euler G, Fuxe K, Tanganelli S, Finnman U-B, Eneroth P (1990) Changes in pituitary-adrenal activity affect the binding properties of striatal dopamine D-2 receptors but not their modulation by neurotensin and cholecystokinin-8. Neurochem Int 16:275–280

    Google Scholar 

  • Fuxe K, Andersson K, Locatelli V, Agnati LF, Hokfelt T, Skirboll L, Mutt V (1980) Cholecystokinin peptides produce marked reduction of dopamine turnover in discrete areas in the rat brain following intraventricular injection. Eur J Pharmacol 67:329–331

    Google Scholar 

  • Fuxe K, Agnati LF, Benfenati F, Cimino M, Algeri S, Hökfelt T, Mutt V (1981) Modulation of cholecystokinins of 3H-spiroperidol binding in rat striatum: evidence for increased affinity and reduction in the number of binding sites. Acta Physiol Scand 113:567–569

    Google Scholar 

  • Fuxe K, Agnati LF, Vanderhaeghen J-J, Tatemoto K, Andersson K, Eneroth P, Harfstrand A, von Euler G, Toni R, Goldstein M, Mutt V (1985) Cholecystokinin neuron systems and their interactions with the presynaptic features of the dopamine neuron systems: A morphometric and neurochemical analysis involving studies on the action of cholecystokinin-8 and cholecystokinin-58. Ann NY Acad Sci USA 448:231–254

    Google Scholar 

  • Hommer D, Skirboll L (1983) Cholecystokinin-like peptides potentiate apomorphine-induced inhibition of dopamine neurons. Eur J Pharmacol 91:151–152

    Google Scholar 

  • Hökfelt T, Rehfelt JF, Skirboll L, Ivemark B, Goldstein M, Markey K (1980) Evidence for coexistence of dopamine and CCK in mesolimbic neurons. Nature 285:476–478

    Google Scholar 

  • Imperato A, Di Chiara G (1988) Effects of locally applied D-1 and D-2 receptor agonists and antagonists studied with brain dialysis. Eur J Pharmacol 156:385–393

    Google Scholar 

  • Lehmann 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 

  • Markstein R, Hökfelt T (1984) Effects of cholecystokinin octapeptide on dopamine release from slices of cat caudate nucleus. J Neurosci 4:570–575

    Google Scholar 

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

    Google Scholar 

  • Roth R (1979) Dopamine autoreceptors: pharmacology, function and comparison with post-synaptic dopamine receptors. Commun Psychopharmacol 3:429–445

    Google Scholar 

  • Ruggeri M, Ungerstedt U, Agnati LF, Mutt V, Harfstrand A, Fuxe K (1987) Effects of cholecystokinin peptides and neurotensin on dopamine release and metabolism in the rostral and caudal part of the nucleus accumbens using intracisternal dialysis in the anaesthetized rat. Neurochem Int 10:509–520

    Google Scholar 

  • Skirboll LR, Grace AA, Bunney BS (1979) Dopamine auto- and post-synaptic receptors: electrophysiological evidence for a differential sensitivity to dopamine agonists. Science 206:80–82

    Google Scholar 

  • Starke K, Göthert M, Kilbinger H (1989) Modulation of neurotransmitter release by presynaptic autoreceptors. Physiol Rev 69:864–989

    Google Scholar 

  • Tanganelli S, von Euler G, Fuxe K, Agnati LF, Ungerstedt U (1989) Neurotensin counteracts apomorphine-induced inhibition of dopamine release as studied by microdialysis in rat neostriatum. Brain Res 502:319–324

    Google Scholar 

  • Ungerstedt U (1984) Measurement of neurotransmitter release by intracranial dialysis. In: Marsden CD (ed) Measurement of neurotransmitter release in vitro. Wiley, New York, pp 81–105

    Google Scholar 

  • Voigt MM, Wang RY (1984) In vivo release of dopamine in the nucleus accumbens of the rat: modulation by cholecystokinin. Brain Res 296:189–193

    Google Scholar 

  • Wang RY (1988) Co-localization of dopamine and cholecystokinin: functional significance. Prog. Catecholamine Res., Part B, Central Aspects. Liss, New York, pp 217–224

    Google Scholar 

  • Watkins LR, Kinscheck IB, Mayer DJ (1984) Potentiation of opiate analgesia and apparent reversal of morphine tolerance by proglumide. Science 224:395–396

    Google Scholar 

  • Watkins LR, Kinscheck IB, Mayer DJ (1985) Potentiation of morphine analgesia by the cholecystokinin antagonist proglumide. Brain Res 327:169–180

    Google Scholar 

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

    Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Additional information

Send offprint requests to K. Fuxe at the above address

Rights and permissions

Reprints and permissions

About this article

Cite this article

Tanganelli, S., Fuxe, K., von Euler, G. et al. Involvement of cholecystokinin receptors in the control of striatal dopamine autoreceptors. Naunyn-Schmiedeberg's Arch Pharmacol 342, 300–304 (1990). https://doi.org/10.1007/BF00169441

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF00169441

Key words

Navigation