Abstract
The α2-adrenoceptor agonist, UK14304, dose-dependently inhibited the electrically stimulated release of dopamine (DA) from rat nucleus accumbens slices. This effect was antagonized by idazoxan, confirming that it was an α2-adrenoceptor mediated effect. There was no evidence of endogenous activation of noradrenergic receptors suggesting that the α2-adrenoceptor agonist was not acting presynaptically to inhibit noradrenaline release. An in vitro superfusion technique was used to investigate wheher there was any interaction between α2-adrenoceptors and DA D2-receptors in mediating their inhibitory effects on [3H]DA release from rat nucleus accumbens slices. α2-Adrenoceptor and DA D2-receptors interact with similar second messenger systems and it was considered that they may compete for a common pool of G-proteins. The inhibitory effects of the α2-adrenoceptor agonist, UK14304, and the DA receptor agonists, quinpirole, apomorphine and pergolide were not independent. However, there was no evidence of any interaction between UK14304 and the DA D2-receptor antagonists, sulpiride or haloperidol, suggesting that the two receptors do not compete for a common pool of G-proteins in mediating their inhibitory effects on DA release.
Similar content being viewed by others
References
Lake, C. R., Pickar, D., Ziegler, M. G., Lipper, S., Slater, S., and Murphy, D. L. 1982. High plasma norepinephrine levels in patients with major affective disorder. Am. J. Psychiatry 139:1315–1318.
De Villiers, A. S., Russell, V. A., Carstens, M. E., Aalbers, C., Gagiano, C. A., Chalton, D. O., and Taljaard, J. J. F. 1987. Noradrenergic function and hypothalamic-pituitary-adrenal axis activity in primary unipolar major depressive disorder. Psychiatry Res. 22:127–140.
Willner, P. 1983. Dopamine and depression: a review of recent evidence. II. Theoretical approaches. Brain Res. Rev. 6:225–236.
Allin, R., Russell, V. A., Lamm, M. C. L., and Taljaard, J. J. F. 1988. Regional distribution of monoamines in the nucleus accumbens of the rat. Neurochem. Res. 13:937–942.
Nurse, B., Russell, V. A., and Taljaard, J. J. F. 1984. 289-1 β-adrenoceptor agonists modulate [3H]dopamine release from rat nucleus accumbens slices: implications for research into depression. Neurochem. Res. 9:1231–1238.
Nurse, B., Russell, V. A., and Taljaard, J. J. F. 1985. Effect of chronic desipramine treatment on adrenoceptor modulation of [3H]dopamine release from rat nucleus accumbens slices. Brain Res. 334:235–242.
Russell, V. A., Nurse, B., Lamm, M. C. L., and Taljaard, J. J. F. 1987. Effect of chronic antidepressant treatment on noradrenergic modulation of [3H]dopamine release from rat nucleus accumbens and striatal slices. Brain Res. 410:78–82.
Cotecchia, S., Kobilka, B. K., Daniel, K. W., Nolan, R. D., Lapetina, E. Y., Caron, M. G., Lefkowitz, R. J., and Regan, J. W. 1990. Multiple second messenger pathways of α-adrenergic receptor subtypes expressed in eukaryotic cells. J. Biol. Chem. 265:63–69.
Cooper, D. M. F., Bier-Laning, C. M., Halford, M. K., Ahlijanian, M. K., and Zahniser, N. R. 1986. Dopamine, acting through D-2 receptors, inhibits rat striatal adenylate cyclase by a GTP-dependent process. Mol. Pharmacol. 29:113–119.
Onali, P., and Olianas, M. C. 1989. Involvement of adenylate cyclase inhibition in dopamine autoreceptor regulation of tyrosine hydroxylase in rat nucleus accumbens. Neurosci. Lett. 102:91–96.
Pizzi, M., Da Prada, M., Valerio, A., Memo, M., Spano, P. F., and Haefely, W. E. 1988. Dopamine D2 receptor stimulation inhibits inositol phosphate generating system in rat striatal slices. Brain Res. 456:235–240.
Williams, J. T., Henderson, G., and North, R. A. 1985. Characterization of α2-adrenoceptors which increase potassium conductance in rat locus coeruleus neurons. Neuroscience 14:95–101.
Tatsumi, H., Costa, M., Schimerlik, M., and North, R. A. 1990. Potassium conductance increased by noradrenaline, opioids, somatostatin, and G-proteins: whole-cell recording from guinea pig submucous neurons. J. Neurosci. 10:1675–1682.
Freedman, J. E., and Weight, F. F. 1988. Single K+ channels activated by D2 dopamine receptors in acutely dissociated neurons from rat corpus striatum. Proc. Natl. Acad. Sci. USA 85:3618–3622.
Drukarch, B., Schepens, E., Schoffelmeer, A. N. M., and Stoof, J. C. 1989. Stimulation of D-2 dopamine receptors decreases the evoked in vitro release of [3H]acetylcholine from rat neostriatum: role of K+ and Ca2+. J. Neurochem. 52:1680–1685.
Sasaki, K., and Sato, M. 1987. A single GTP-binding protein regulates K+ channels coupled with dopamine, histamine and acetylcholine receptors. Nature 325:259–262.
Vallar, L., and Meldolesi, J. 1989. Mechanisms of signal transduction at the dopamine D2 receptor. Trends Pharmacol. Sci. 10:74–77.
Drukarch, B., Schepens, E., and Stoff, J. C. 1990. Muscarinic receptor activation attenuates D2 dopamine receptor mediated inhibition of acetylcholine release in rat striatum: indications for a common signal transduction pathway. Neuroscience 37:1–9.
Allgaier, C., Daschmann, B., Sieverling, J., and Hertting, G. 1989. Presynaptic κ-opioid receptors on noradrenergic nerve terminals couple to G proteins and interact with the α2-adrenoceptor. J. Neurochem. 53:1629–1635.
Cambridge, D. 1981. UK 14,304, a potent and selective α2 agonist for the characterization of α-adrenoceptor subtypes. Eur. J. Pharmacol. 72:413–415.
Reyneke, L., Allin, R., Russell, V. A., and Taljaard, J. J. F. 1989. Lack of effect of chronic desipramine treatment on dopaminergic activity in the nucleus accumbens of the rat. Neurochem. Res. 14:661–665.
Hetey, L., and Zimmerman, B. 1986. Characterization of the synaptosomal high-affinity uptake of noradrenaline in the nucleus accumbens of rats. Biomed. Biochim. Acta 45:1203–1207.
Hyttel, J., and Larsen, J.-J. 1985. Serotonin-selective antidepressants. Acta Pharmacol. Toxicol. 56:146–153.
Bonnet, J. J., Chagraoui, A., Protais, P., Costentin, J. 1987. Interactions of amineptine with the neuronal dopamine uptake system: neurochemical in vitro and in vivo studies. J. Neural Transm. 69:211–220.
Freedman, J. E., and Aghajanian, G. K. 1984. Idazoxan (RX 781094) selectively antagonizes α2-adrenoceptors on rat central neurons. Eur. J. Pharmacol. 105:265–272.
Molderings, G. J., and Göthert, M. 1990. Mutual interaction between presynaptic α2-adrenoceptors and 5-HT1B receptors on the sympathetic nerve terminals of the rat inferior vena cava. Naunyn-Schmiedeberg's Arch. Pharmacol. 341:391–397.
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Russell, V.A., Lamm, M.C.L. & Taljaard, J.J.F. Lack of interaction between α2 and dopamine D2-receptors in mediating their inhibitory effects on [3H]dopamine release from rat nucleus accumbens slices. Neurochem Res 18, 285–289 (1993). https://doi.org/10.1007/BF00969084
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF00969084