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The CRF1 receptor antagonist, antalarmin, reverses isolation-induced up-regulation of dopamine D2 receptors in the amygdala and nucleus accumbens of fawn-hooded rats

Authors

  • Elvan Djouma,

    1. Department of Pharmacology, Monash University, Clayton, Victoria 3800, Australia
    2. Brain Injury and Repair Group, Howard Florey Institute, Royal Parade, Parkville, Victoria 3010, Australia
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  • Katie Card,

    1. Department of Pharmacology, Monash University, Clayton, Victoria 3800, Australia
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  • Daniel J. Lodge,

    1. Department of Pharmacology, Monash University, Clayton, Victoria 3800, Australia
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    • *

      Present address: Department of Neuroscience, University of Pittsburgh, PA, USA.

  • Andrew J. Lawrence

    1. Brain Injury and Repair Group, Howard Florey Institute, Royal Parade, Parkville, Victoria 3010, Australia
    2. Centre for Neuroscience, University of Melbourne, Parkville, Victoria 3010, Australia
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Dr Andrew J. Lawrence, 1Brain Injury and Repair Group, as above.
E-mail: Andrew.Lawrence@hfi.unimelb.edu.au

Abstract

We have previously shown that Fawn-Hooded (FH) rats reared in isolation display an anxiety-like phenotype and an enhanced acquisition of ethanol seeking behaviour. Furthermore, antalarmin, a selective corticotrophin-releasing factor type 1 (CRF1) receptor antagonist, reduces isolation-induced acquisition and maintenance of volitional ethanol consumption in this strain. The aim of this study was to investigate the ability of CRF1 receptor antagonism by antalarmin to impact upon brain chemistry in both isolated and group-housed FH rats. To achieve this, FH rats were reared, from weaning, in either group-housed or isolation-housed conditions and at 12 weeks of age were treated with antalarmin (20 mg/kg, i.p; n = 10 per group) or vehicle (1 mL/kg, i.p; n = 10 per group) bi-daily for ten consecutive days before being killed and their brains removed for neurochemical analyses. Autoradiography and in situ hybridization was employed to analyse changes in the dopaminergic and neurotrophin systems. Isolation rearing increased dopamine D2 receptor density in the central amygdala and nucleus accumbens, an effect reversed by antalarmin treatment. Conversely, treatment with antalarmin had no impact upon the isolation-induced alterations of the mRNA encoding brain-derived neurotrophic factor or the TrkB receptor. Collectively, these findings demonstrate that multiple signalling systems are susceptible to modulation by social isolation and that antalarmin can reverse some, but not all, isolation-induced alterations in brain chemistry.

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