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Convulsant Doses of a Dopamine D1 Receptor Agonist Result in Erk-Dependent Increases in Zif268 and Arc/Arg3.1 Expression in Mouse Dentate Gyrus

By Giuseppe Gangarossa, Manuela Di Benedetto, Gerard J. O'Sullivan, Mark Dunleavy, Cristina Alcacer, Alessandra Bonito-Oliva, David C. Henshall, John L. Waddington, Emmanuel Valjent and Gilberto Fisone

Abstract

Activation of dopamine D1 receptors (D1Rs) has been shown to induce epileptiform activity. We studied the molecular changes occurring in the hippocampus in response to the administration of the D1-type receptor agonist, SKF 81297. SKF 81297 at 2.5 and 5.0 mg/kg induced behavioural seizures. Electrophysiological recordings in the dentate gyrus revealed the presence of epileptiform discharges peaking at 30–45 min post-injection and declining by 60 min. Seizures were prevented by the D1-type receptor antagonist, SCH 23390, or the cannabinoid CB1 receptor agonist, CP 55,940. The effect of SKF 81297 was accompanied by increased phosphorylation of the extracellular signal-regulated protein kinases 1 and 2 (ERK), in the granule cells of the dentate gyrus. This effect was also observed in response to administration of other D1-type receptor agonists, such as SKF83822 and SKF83959. In addition, SKF 81297 increased the phosphorylation of the ribosomal protein S6 and histone H3, two downstream targets of ERK. These effects were prevented by genetic inactivation of D1Rs, or by pharmacological inhibition of ERK. SKF 81297 was also able to enhance the levels of Zif268 and Arc/Arg3.1, two immediate early genes involved in transcriptional regulation and synaptic plasticity. These changes may be involved in forms of activity-dependent plasticity linked to the manifestation of seizures and to the ability of dopamine to affect learning and memory

Topics: Research Article
Publisher: Public Library of Science
OAI identifier: oai:pubmedcentral.nih.gov:3086923
Provided by: PubMed Central
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    1. (1994). Activation of pirenzepine-sensitive muscarinic receptors induces a specific pattern of immediate-early gene expression in rat brain neurons.
    2. (1992). Activation of the zinc finger encoding gene krox-20 in adult rat brain: comparison with zif268.
    3. (2002). Acute neuronal injury, excitotoxicity, and the endocannabinoid system.
    4. (2003). CB1 cannabinoid receptors and on-demand defense against excitotoxicity.
    5. (1988). Convulsantinduced increase in transcription factor messenger RNAs in rat brain.
    6. Corces VG (2004) Phosphorylation of histone H3: a balancing act between chromosome condensation and transcriptional activation.
    7. (1992). Correlation between the induction of an immediate early gene, zif/268, and long-term potentiation in the dentate gyrus.
    8. (1998). DARPP-32: regulator of the efficacy of dopaminergic neurotransmission.
    9. (1990). Differential expression of immediate early genes in the hippocampus and spinal cord.
    10. (1991). Differential expression of immediate early genes in the hippocampus in the kindling model of epilepsy.
    11. (2008). Dynamic seizure-related changes in extracellular signal-regulated kinase activation in a mouse model of temporal lobe epilepsy.
    12. (2005). Ethological resolution of behavioural topography and D1-like versus D2-like agonist responses in congenic D5 dopamine receptor mutants: identification of D5:D2-like interactions.
    13. (2005). Fluoro-Jade C results in ultra high resolution and contrast labeling of degenerating neurons.
    14. (1987). Generalized seizures induce c-fos protein(s) in mammalian neurons.
    15. (1988). High-frequency discharge of dentate granule cells, but not long-term potentiation, induces c-fos protein.
    16. (1993). Identification of p42 mitogen-activated protein kinase as a tyrosine kinase substrate activated by maximal electroconvulsive shock in hippocampus.
    17. (2000). Involvement of the extracellular signal-regulated kinase cascade for cocainerewarding properties.
    18. (1987). Kindling stimulation induces c-fos protein(s) in granule cells of the rat dentate gyrus.
    19. (1987). Mapping patterns of cfos expression in the central nervous system after seizure.
    20. (1998). Mitogen-activated protein kinase is increased in the limbic structures of the rat brain during the early stages of status epilepticus.
    21. (2003). MSK1 and MSK2 mediate mitogen- and stress-induced phosphorylation of histone H3: a controversy resolved. Sci STKE
    22. (1979). Multiple phosphorylation of ribosomal protein S6 during transition of quiescent 3T3 cells into early G1, and cellular compartmentalization of the phosphate donor.
    23. (2009). Novel translational control in Arc-dependent long term potentiation consolidation in vivo.
    24. (2005). Parsing molecular and behavioral effects of cocaine in mitogen- and stressactivated protein kinase-1-deficient mice.
    25. (1998). Patterns of status epilepticus-induced neuronal injury during development and long-term consequences.
    26. (2008). Perturbation of syndapin/PACSIN impairs synaptic vesicle recycling evoked by intense stimulation.
    27. (1994). Phosphorylation and activation of mitogen-activated protein kinase by kainic acid-induced seizure in rat hippocampus.
    28. (1999). Pitkanen A
    29. (1989). Rapid increase of an immediate early gene messenger RNA in hippocampal neurons by synaptic NMDA receptor activation.
    30. (1990). Rapid rise in transcription factor mRNAs in rat brain after electroshock-induced seizures.
    31. (2005). Regulation of a protein phosphatase cascade allows convergent dopamine and glutamate signals to activate ERK in the striatum.
    32. (2006). Ribosomal protein S6 phosphorylation: from protein synthesis to cell size.
    33. (1993). Seizure promotion by D1 agonists does not correlate with other dopaminergic properties.
    34. (2002). Seizure-induced neuronal injury: animal data.
    35. (2000). Status epilepticusinduced neuronal loss in humans without systemic complications or epilepsy.
    36. (2008). The immediate early gene arc/arg3.1: regulation, mechanisms, and function.
    37. (2000). The MAPK/ERK cascade targets both Elk-1 and cAMP response element-binding protein to control long-term potentiation-dependent gene expression in the dentate gyrus in vivo.
    38. (2007). The nuclear kinase mitogen- and stress-activated protein kinase 1 regulates hippocampal chromatin remodeling in memory formation.
    39. (2002). The role of muscarinic acetylcholine receptor-mediated activation of extracellular signal-regulated kinase 1/2 in pilocarpine-induced seizures.

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