¹Department of Neurosurgery, Farber Institute for Neurosciences, Thomas Jefferson University, Philadelphia, PA, USA

Correspondence: Dr CA Rudoy, Department of Neurosurgery, Farber Institute for Neurosciences, Thomas Jefferson University, 900 Walnut Street, Room 417, Philadelphia, PA 19107, USA, Tel: +1 215 503 5870, Fax: +1 215 503 9238, E-mail: carla.rudoy@jefferson.edu

Received 15 December 2007; Revised 27 May 2008; Accepted 30 May 2008; Published online 2 July 2008.

Abstract

We previously showed that betaxolol, a selective ₁-adrenergic receptor antagonist, administered during early phases of cocaine abstinence, ameliorated withdrawal-induced anxiety and blocked increases in amygdalar 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 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 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 ₁-adrenergic receptor, modulation of its downstream cell-signaling elements and CRF gene expression.