(3,4-Dihydroxyphenylimino)-2-Imidazoline (DPI) and Its Action at Noradrenergic and Dopaminergic Receptors in the Nucleus Accumbens of Rats: Mesolimbic Catecholamine Receptors and Hyperactivity

  • A. R. Cools
  • S. K. Oosterloo
Conference paper
Part of the Journal of Neural Transmission book series (NEURAL SUPPL, volume 18)


Bilateral administration of ergometrine into the nucleus accumbens of rats pretreated 1–3 min earlier with intra-accumbens injections of noradrenaline, phenylephrine, clonidine and phentolamine has been found to produce a normal ergometrine-induced hyperactivity. In contrast, low doses of dopamine and (3,4-dihydroxyphenylimino)-2-imidazoline (DPI) and only high doses of clonidine and phentolamine have been found to attenuate the ergometrine response. These data together with the finding that phentolamine is unable to alter DPI’s ability to suppress the ergometrine response provide direct evidence that the latter DPI effect is certainly not due to its ability to act as an agonist at α-NE receptors within the nucleus accumbens of rats.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. Bell, C., Conway, E. L., Lan and W. L.: Ergometrine and apomorphine as selective antagonists of dopamine in the canine renal musculature. Pharmac. 52, 591–595 (1974).Google Scholar
  2. Blackburn, K.J., Bremner, R. M., Greengrass, P. M., Morville, M.: Selective affinities of bromocriptine and lergotrile for rat limbic dopamine binding sites. Br. J. Pharmac. 64, 413 P (1978).Google Scholar
  3. Mesolimbic Catecholamine Receptors, DPI and Hyperactivity in Rats 187Google Scholar
  4. Cerletti, A., Doefner, W.: Comparative study on the serotonin antagonism of amide derivatives of lysergic acid and ergot alkaloids. J. Pharmacol. exp. Ther. 122, 124–138 (1958).PubMedGoogle Scholar
  5. Cools, A.R.: Two functionally and pharmacologically distinct dopamine receptors in the rat brain. Adv. Biochem. Pharmacol. 16, 215–225 (1977 a).Google Scholar
  6. Cools, A.R.: Basic considerations of the role of concertedly working dopaminergic, GABA-ergic, cholinergic and serotonergic mechanisms within the neostriatum and nucleus accumbens in locomotor activity, stereotyped gnawing, turning and dyskinetic activities. In: Advances in Behavioural Biology, Vol. 21 (Proceedings of Symposium on Contemporary Issues in Stimulant Research, Durham 1975), pp. 98–142. New York: Plenum Publishing Corporation. 1977 b.Google Scholar
  7. Cools, A.R.: Ergometrine and its biphasic action at dopaminergic receptors in the nucleus accumbens of rats. Pharmacology 16, suppl. 1, 9–14 (1978).Google Scholar
  8. Cools, A.R., Honig, W. M. M., Pijnenburg, A.J.J., Van Rossum, J. M.: The nucleus accumbens of rats and dopaminergic mechanisms regulating locomotor behaviour. Neurosci. Letters 3, 335–339 (1976 a).Google Scholar
  9. Cools, A.R., Struyker Boudier, H. A.J., Van Rossum, J M.: Dopamine receptors: selective agonists and antagonists of functionally distinct types within the feline brain. Europ. J. Pharmacol. 37, 283–293 (1976 b).Google Scholar
  10. Cools, A. R., Van Rossum, J. M.: Multiple receptors for brain dopamine in behavioural regulation: concept of dopamine-e and dopamine-i receptors. Life Sci. 27, 1237–1253 (1980).Google Scholar
  11. Costall, B., Naylor, R.J.: Apomorphine as an antagonist of the dopamine response from the nucleus accumbens. J. Pharm. Pharmacol. 28, 592–595 (1976).CrossRefPubMedGoogle Scholar
  12. Costall, B., Hui, S.-C. G., Naylor, R.J.: The importance of serotonergic mechanisms for the induction of hyperactivity by amphetamine and its antagonism by intra-accumbens (3,4-dihydroxy-phenylamino)-2imidazole (DPI). Neuropharmacol. 18, 605–609 (1979).CrossRefGoogle Scholar
  13. Drummond, A., Bucher, F., Levitan,J.: LSD labels as novel dopamine receptor in molluscan nervous system. Nature 272, 368–370 (1978).CrossRefPubMedGoogle Scholar
  14. König, F. R.J., Klippel, R. R.: The Rat Brain. Baltimore: Williams and Wilkins. 1963.Google Scholar
  15. Megens, A. A. P. H., Cools, A.R.: Presence of a particular subpopulation of dopamine receptors within the septal nuclei: a behavioural study on cats. Europ. J. Pharmacol. 71, 247–258 (1981).CrossRefGoogle Scholar
  16. Pijnenburg, A.J.J., Woodruff, G. N., Van Rossum, J. M.: Ergometrine induced locomotor activity following intracerebral injection into the nucleus accumbens. Brain Res. 59, 289–302 (1973).CrossRefPubMedGoogle Scholar
  17. Pijnenburg, A.J.J., Honig, W. M. M., Van Rossum, J. M.: Effects of antagonists upon locomotor stimulation induced by injection of dopamine and noradrenaline into the nucleus accumbens of nialamide-pretreated rats. Psychopharmacologia (Berl.) 41, 175–180 (1975).Google Scholar
  18. Pijnenburg, A.J.J., Honig, W. M. M., Struyker Boudier, H. A.J., Cools, A. R., Van der Heyden, J.A. M., Van Rossum, J M.: Further investigations on the effects of ergometrine and other ergot derivatives following injection into the nucleus accumbens of rats. Arch. in Pharmacodyn. 222, 103–115 (1976 a).Google Scholar
  19. Pijnenburg, A.J.J., Honig, W. M. M., Van der Heyden, J. A. M., Von Rossum, J. M.: Effects of chemical stimulation of the mesolimbic dopamine system upon locomotor activity. Europ. J. Pharmacol. 35, 45–58 (1976 b).Google Scholar
  20. Ruffolo, R. R., jr., Yaden, E. L., Waddell, J. E., Dillard, R. D.: Receptor interactions of imidazolines. VI. Significance of carbon bridge separating phenyl and imidazoline rings of tolazoline-like alpha adrenergic imidazolines. J. Pharmacol. exp. Ther. 214, 535–540 (1980).PubMedGoogle Scholar
  21. Springer, J., Hannigan, J. H., jr., Isaacson, R. L.: Changes in dopamine and DOPAC following systemic administration of apomorphine and 3,4-dihydroxyphenylamino-2-imidazoline (DPI) in rats. Brain Res. 220, 226–230 (1981).CrossRefPubMedGoogle Scholar
  22. Struyker Boudier, H., Gielen, W., Cools, A.R., Van Rossum, J M.: Pharmacological analysis of dopamine-induced inhibition and excitation of neurones of the snail Helix aspersa. Arch. int. Pharmacodyn. 209, 324–331 (1974).Google Scholar
  23. Struyker Boudier, H., De Boer, J., Smeets, G., Lien, E., Van Rossum, J. M.: Structure-activity relationships for central and peripheral a-adrenergic activity of imidazoline derivatives. Life Sci. 17, 377–386 (1975 a).Google Scholar
  24. Struyker Boudier, H., Teppema, L., Cools, A.R., Van Rossum, J M.: (3,4-dihydroxyphenylamino)-2-imidazoline (DPI), a new potent agonist at dopamine receptors mediating neuronal inhibition. J. Pharm. Pharmacol. 27, 882–883 (1975 b).Google Scholar
  25. Woodman, O. L., Medgett, I. C., Lang, W J, Rand, M.J.: Agonistic actions of DPI on a-adrenoceptors and dopamine receptors. Europ. J. Pharmacol. 75, 11–20 (1981).CrossRefGoogle Scholar

Copyright information

© Springer-Verlag Wien 1983

Authors and Affiliations

  • A. R. Cools
    • 1
  • S. K. Oosterloo
    • 2
  1. 1.Department of PharmacologyUniversity of NijmegenNijmegenThe Netherlands
  2. 2.Department of PharmacologyUniversity of NijmegenNijmegenThe Netherlands

Personalised recommendations