Elsevier

Neuroscience

Volume 117, Issue 2, 21 March 2003, Pages 243-247
Neuroscience

Letter to neuroscience
The CRF1 receptor antagonist antalarmin reduces volitional ethanol consumption in isolation-reared fawn-hooded rats

https://doi.org/10.1016/S0306-4522(02)00793-5Get rights and content

Abstract

Corticotropin releasing factor is a neuropeptide associated with the integration of physiological and behavioural responses to stress. More recently, corticotropin releasing factor has been implicated in the actions of abused drugs, including ethanol. Moreover, previous studies have demonstrated that the non-selective corticotropin releasing factor receptor antagonist, α-helical corticotropin releasing factor9-41, can diminish some of the behavioural effects associated with ethanol withdrawal, whilst the selective corticotropin releasing factor1 receptor antagonist CP-154,526 has been beneficial in decreasing stress-induced relapse into alcohol-seeking behaviour. However, as yet the ability of selective corticotropin releasing factor compounds to modulate volitional ethanol consumption has not been investigated. For these reasons the present study aims to examine the effects of antalarmin, a selective, centrally acting corticotropin releasing factor1 receptor antagonist, on both the initiation and maintenance of ethanol consumption in isolation-reared Fawn-Hooded rats. Here we demonstrate that whilst both antalarmin and diazepam can decrease the acquisition of an ethanol-preferring phenotype by Fawn-Hooded rats, only antalarmin can alter established, volitional ethanol consumption. This ability of antalarmin to reduce established ethanol consumption is apparently unrelated to changes in ingestive behaviour, or a generalised anxiolytic action. For these reasons, such drugs may provide a new therapeutic approach for the treatment of alcoholism; however, this requires further investigation.

Section snippets

Experimental procedures

All experiments were performed in accordance with the Prevention of Cruelty to Animals Act 1986 under the guidelines of the National Health and Medical Research Council Code of Practise for the Care and Use of Animals for Experimental Purposes in Australia (NHMRC, 1997). All attempts were made to minimise the number of animals used and their suffering.

All rats were individually housed upon weaning (3 weeks of age) in the Department of Pharmacology, Monash University animal house, and kept at

Results

Antalarmin induced a significant anxiolytic phenotype comparable to that of diazepam as determined by an increased time spent on the open arms of the elevated plus-maze (Fig. 1a), whilst having no sedative or locomotive effects as determined by no change in total arm entries (Fig. 1b). In addition, acute pre-treatment (3 days) with either antalarmin or diazepam reduced the acquisition of voluntary ethanol consumption (defined as ethanol intake over 2.5 g/kg/day) when compared with

Discussion

Here we demonstrate for the first time that whilst both diazepam and antalarmin were beneficial in decreasing the acquisition of an ethanol-preferring phenotype in isolation-reared FH rats, only antalarmin was able to affect established, volitional ethanol consumption. This effect is specific to antalarmin and not generalised to all anxiolytics since chronic diazepam treatment had no effect on established ethanol-seeking behaviour. Previous reports have demonstrated that CRF agonists display

Acknowledgements

The authors would like to acknowledge discussions with Professor Bill Blessing, Dr. B. J. Canny and thank Dr. G. P. Chrousos for the generous gift of antalarmin.

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