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Interdependent Adrenergic Receptor Regulation of Arc and Zif268 mRNA in Cerebral Cortex

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Interdependent Adrenergic Receptor Regulation of Arc and Zif268 mRNA in Cerebral Cortex

Norah Essali et al. Neurosci Lett.

Abstract

Norepinephrine is a neurotransmitter that signals by stimulating the α1, α2 and β adrenergic receptor (AR). We determined the role of these receptors in regulating the immediate early genes, Activity Regulated Cytoskeleton Associated Protein (Arc) and Zif268 in the rat cerebral cortex. RX821002, an α2-AR antagonist, produced Arc and Zif268 elevations across cortical layers. Next we examined the effects of delivering RX821002 with an α1-AR antagonist, prazosin, and a β-AR antagonist, propranolol. RX821002 given with a prazosin and propranolol cocktail, or with each of these antagonists individually, decreased Arc and Zif268 to saline-treated control levels in most cortical layers. Arc and Zif268 levels were also similar to saline-treated control levels when rats were given a prazosin and propranolol cocktail alone, or when each of these antagonists were delivered individually. Taken together, these data reveal that α2-AR uniquely exert a tonic inibitory regulation of both Arc and Zif268 compared to α1 and β-AR. However, the ability of RX821002 to increase Arc and Zif268 is interdependent with α1 and β-AR signaling.

Keywords: Adrenergic; Arc; Cortex; Norepinephrine; Zif268.

Conflict of interest statement

Disclosures: The authors declare no conflict of interest, financial or otherwise.

Figures

Figure 1
Figure 1. In situ hybridization autoradiographs for Arc
These images correspond to 0.7 mm anterior to bregma in adult animals. The greatest enrichment for Arc mRNA is seen in layers 4 and 6. RX821002 causes increases in Arc mRNA that are blocked by co-administration of prazosin and propranolol. The scale bar indicates the density of mRNA calibrated for nCi/mg tissue.
Figure 2
Figure 2. The effects of RX821002 (5mg/kg) alone, or combined with prazosin (15mg/kg) and propranolol (10mg/kg), or the effects of prazosin and propranolol cocktail on Arc (A) and Zif268 (B) expression
Graph shows changes in Arc and Zif268 1hr after administration of adrenergic receptor antagonists. Each graph shows percent change in IEG levels relative to saline treated controls. Data are quantified according to cortical layer and analyzed by two-way anova with Bonferroni post-test. *p<0.05, ***p<0.001: significantly different from control.
Figure 3
Figure 3. The effects of RX821002 (5mg/kg) alone, or combined with prazosin (15mg/kg) or propranolol (10mg/kg) individually, or the effects of prazosin or propranolol individually on Arc (A) and Zif268 (B) expression
Graph shows changes in Arc and Zif268 1hr after administration of adrenergic receptor antagonists. Each graph shows percent change in IEG levels relative to saline treated controls. Data are quantified according to cortical layer and analyzed by two-way anova with Bonferroni post-test. *p<0.05, **P<0.01, ***p<0.001: significantly different from control.

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