The atypical dopamine D1 receptor agonist SKF 83959 induces striatal Fos expression in rats

The atypical dopamine D1 receptor agonist SKF 83959 induces striatal Fos expression in rats The effects of dopamine D1 receptor agonists are often presumed to result from an activation of adenylyl cyclase, but dopamine D1 receptors may also be linked to other signal transduction cascades and the relative importance of these various pathways is currently unclear. SKF 83959 is an agonist at dopamine D1 receptors linked to phospholipase C, but has been reported to be an antagonist at receptors linked to adenylyl cyclase. The current report demonstrates that SKF 83959 induces pronounced, nonpatchy, expression of the immediate-early gene product Fos in the striatum of intact rats which can be converted to a patchy pattern by pretreatment with the dopamine D2-like receptor agonist quinpirole. In rats with unilateral 6-hydroxydopamine lesions SKF 83959 induces strong behavioral rotation and a greatly potentiated Fos response. All of the responses to SKF 83959, in both intact and dopamine-depleted animals, can be blocked by pretreatment with the dopamine D1 receptor antagonist SCH-23390. In intact subjects, SKF 83959 induced Fos expression less potently than the standard dopamine D1 receptor agonist SKF 82958, but the two drugs were approximately equipotent in deinnervated animals. These results demonstrate for the first time that possession of full efficacy at dopamine D1 receptors linked to adenylyl cyclase is not a necessary requirement for the induction of striatal Fos expression in intact animals and suggest that alternative signal transduction pathways may play a role in dopamine agonist induced Fos expression, especially in dopamine-depleted subjects. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png European Journal of Pharmacology Elsevier

The atypical dopamine D1 receptor agonist SKF 83959 induces striatal Fos expression in rats

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Publisher
Elsevier
Copyright
Copyright © 2005 Elsevier B.V.
ISSN
0014-2999
D.O.I.
10.1016/j.ejphar.2005.11.003
Publisher site
See Article on Publisher Site

Abstract

The effects of dopamine D1 receptor agonists are often presumed to result from an activation of adenylyl cyclase, but dopamine D1 receptors may also be linked to other signal transduction cascades and the relative importance of these various pathways is currently unclear. SKF 83959 is an agonist at dopamine D1 receptors linked to phospholipase C, but has been reported to be an antagonist at receptors linked to adenylyl cyclase. The current report demonstrates that SKF 83959 induces pronounced, nonpatchy, expression of the immediate-early gene product Fos in the striatum of intact rats which can be converted to a patchy pattern by pretreatment with the dopamine D2-like receptor agonist quinpirole. In rats with unilateral 6-hydroxydopamine lesions SKF 83959 induces strong behavioral rotation and a greatly potentiated Fos response. All of the responses to SKF 83959, in both intact and dopamine-depleted animals, can be blocked by pretreatment with the dopamine D1 receptor antagonist SCH-23390. In intact subjects, SKF 83959 induced Fos expression less potently than the standard dopamine D1 receptor agonist SKF 82958, but the two drugs were approximately equipotent in deinnervated animals. These results demonstrate for the first time that possession of full efficacy at dopamine D1 receptors linked to adenylyl cyclase is not a necessary requirement for the induction of striatal Fos expression in intact animals and suggest that alternative signal transduction pathways may play a role in dopamine agonist induced Fos expression, especially in dopamine-depleted subjects.

Journal

European Journal of PharmacologyElsevier

Published: Dec 28, 2005

References

  • Quinpirole attenuates the striatal immediate early gene expression, but not the hyperactivity, induced by the serotonin agonist RU-24969
    Cook, D.F.; Wirtshafter, D.
  • SKF 83959 is an antagonist of dopamine D1-like receptors in the prefrontal cortex and nucleus accumbens: a key to its antiparkinsonian effect in animals
    Cools, A.R.; Lubbers, L.; van Oosten, R.V.; Andringa, G.
  • Rotational behavior induced by 8-hydroxy-DPAT, a putative 5HT-1A agonist, in 6-hydroxydopamine rats
    Gerber, R.; Altar, C.A.; Liebman, J.M.
  • Inducible and constitutive transcription factors in the mammalian nervous system: control of gene expression by Jun, Fos and Krox and CREB/ATF proteins
    Herdegen, T.; Leah, J.D.
  • Multiple receptors for dopamine
    Kebabian, J.W.; Calne, D.B.
  • Receptor affinities of dopamine D1 receptor-selective novel phenylbenzazepines
    Neumeyer, J.L.; Kula, N.S.; Bergman, J.; Baskessarini, R.J.
  • Quinpirole attenuates the striatal Fos expression induced by escape behavior
    Struthers, W.M.; Wirtshafter, D.
  • Regulation of the ERK subgroup of MAP kinase cascades through G protein-coupled receptors
    Sugden, P.H.; Clerk, A.
  • NMDA and D1 receptors regulate the phosphorylation of CREB and the induction of c-fos in striatal neurons in primary culture
    Vincent, S.R.; Das, S.; Grunert, M.; WIlliams, L.; Vincent, S.R.

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