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Evidence for beta(1)-Adrenergic Receptor Involvement in Amygdalar Corticotropin-Releasing Factor Gene Expression: Implications for Cocaine Withdrawal
Journal article   Open access   Peer reviewed

Evidence for beta(1)-Adrenergic Receptor Involvement in Amygdalar Corticotropin-Releasing Factor Gene Expression: Implications for Cocaine Withdrawal

Carla A. Rudoy, Arith-Ruth S. Reyes and Elisabeth J. Van Bockstaele
Neuropsychopharmacology (New York, N.Y.), v 34(5), pp 1135-1148
01 Apr 2009
PMID: 18596687
url
https://doi.org/10.1038/npp.2008.102View
Published, Version of Record (VoR) Open

Abstract

Life Sciences & Biomedicine Neurosciences Neurosciences & Neurology Pharmacology & Pharmacy Psychiatry Science & Technology
We previously showed that betaxolol, a selective beta(1)-adrenergic receptor antagonist, administered during early phases of cocaine abstinence, ameliorated withdrawal-induced anxiety and blocked increases in amygdalar beta(1)-adrenergic receptor expression in rats. Here, we report the efficacy of betaxolol in reducing increases in gene expression of amygdalar corticotropin-releasing factor (CRF), a peptide known to be involved in mediating 'anxiety-like' behaviors during initial phases of cocaine abstinence. We also demonstrate attenuation of an amygdalar beta(1)-adrenergic receptor-mediated cell-signaling pathway following this treatment. Male rats were administered betaxolol at 24 and 44 h following chronic cocaine administration. Animals were euthanized at the 48-h time point and the amygdala was microdissected and processed for quantitative reverse transcriptase-polymerase chain reaction and/or western blot analysis. Results showed that betaxolol treatment during early cocaine withdrawal attenuated increases in amygdalar CRF gene expression and cyclic adenosine monophosphate-dependent protein kinase regulatory and catalytic subunit (nuclear fraction) protein expression. Our data also reveal that beta(1)-adrenergic receptors are on amygdalar neurons, which are immunoreactive for CRF. The present findings suggest that the efficacy of betaxolol treatment on cocaine withdrawal-induced anxiety may be related, in part, to its effect on amygdalar beta(1)-adrenergic receptor, modulation of its downstream cell-signaling elements and CRF gene expression.

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