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Regulation of Neuronal Activation by Alpha2A Adrenergic Receptor Agonist

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Abstract

Stress factors induce neuronal activation in brain areas that are related to anxiety and fear. High doses of caffeine induce neuronal activation with Ca2+ influx followed by expression of the immediate early gene c-fos. In the present study, we investigated c-Fos protein expression in stress-responsive brain areas induced by caffeine, as well as the role of alpha2A receptor in the regulation of neuronal activation. Immunohistochemical analysis showed that an acute effect of caffeine induced c-Fos protein expression in the hippocampus, the bed nucleus of stria terminalis (BNST), the lateral septum, the basolateral and central amygdala, the paraventricular hypothalamic nucleus (PVN), the locus coeruleus, and the lateral parabrachial nucleus (LPBN). However, c-Fos expression was attenuated after repeated treatment of caffeine, spaced 24 h apart, compared to a single acute effect. Alpha2A receptor activation with the agonist guanfacine attenuated the acute effect of caffeine in terms of c-Fos expression in neurons in the CA1–CA3 areas of hippocampus, the locus coeruleus and the LPBN as compared with effect of caffeine alone, whereas the number of c-Fos expressing neurons increased in the lateral septum, the dorsal BNST, the central amygdala, and the PVN, areas that are densely innervated by noradrenergic neurons. Guanfacine alone induced c-Fos protein expression in neurons in the central amygdala, the dorsal BNST, the PVN, the LPBN, and the caudal nucleus of the solitary tract. Guanfacine alone also induced phosphorylation of extracellular signal-regulated kinase 1/2 (ERK1/2) in neurons expressing c-Fos in the dorsal BNST, the central amygdala, and the LPBN. These results suggest that alpha2A receptor activation modulates synaptic transmission in neuronal circuits that are correlated with stress in vivo.

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Abbreviations

AR:

Adrenergic receptor

BLA:

Basolateral amygdala

CeA:

Central amygdala

CBP:

CREB binding protein

CREB:

Cyclic-AMP response element binding protein

CREST:

Calcium-responsive transactivator

CRF:

Corticotropin-releasing factor

BNST:

Bed nucleus of the stria terminalis

DG:

Dentate gyrus

ERK1/2:

Extracellular signal-regulated kinase 1/2

LC:

Locus coeruleus

LH:

Lateral hypothalamus

LPBN:

Lateral parabrachial nucleus

NST:

Nucleus of the solitary tract

PVN:

Paraventricular hypothalamic nucleus

PVT:

Paraventricular thalamic nucleus

TH:

Tyrosine hydroxylase

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Acknowledgments

The authors would like to thank Prof. Clark M. Blatteis for his helpful review of the manuscript and constructive comments. This research supported in part by DC000353 to J.D.B.

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  1. Department of Anatomy & Neurobiology, University of Tennessee Health Science Center, 855 Monroe Avenue, Memphis, TN, 38103, USA

    Valentina L. Savchenko & John D. Boughter Jr.

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  1. Valentina L. Savchenko
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  2. John D. Boughter Jr.
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Correspondence to Valentina L. Savchenko.

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Savchenko, V.L., Boughter, J.D. Regulation of Neuronal Activation by Alpha2A Adrenergic Receptor Agonist. Neurotox Res 20, 226–239 (2011). https://doi.org/10.1007/s12640-010-9236-5

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  • DOI: https://doi.org/10.1007/s12640-010-9236-5

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