Worried about that deadline you have to meet? Fancy a beer to help you cope with stress? This reaction might seem exclusive to humans but, as a recent paper in Science shows, something similar is observed in mice that lack a receptor for corticotropin-releasing hormone (CRH).
Alcoholism depends on both environmental and genetic factors. It is well known that stress can have a profound influence on alcohol intake, and some studies have implicated the CRH system in stress-induced alcohol drinking. Sillaber et al. followed this lead and measured voluntary alcohol intake in mice lacking the CRH1 receptor, testing whether stress had any effect on drinking behaviour. They found that, under basal conditions, the knockout mice did not drink more alcohol than their wild-type littermates. However, after repeated stress, the knockout mice started to drink more alcohol on a regular basis. Intriguingly, this behavioural change was not observed immediately after the stressful events; it developed gradually over several weeks and lasted for at least six months, even when the animals were not confronted with any further stressful experience.
As glutamate-mediated neurotransmission has also been implicated in stress-induced alcohol drinking, Sillaber et al. looked for changes in this system that might help to explain the behavioural response of the knockout mice. They found that the NMDA (N-methyl-d-aspartate) receptor subunit NR2B was upregulated in the hippocampus and nucleus accumbens of these animals.
The results of Sillaber et al. point to the CRH1 and NR2B receptors as possible risk factors for alcoholism, but they actually raise more questions than they answer. Why does stress elicit such a delayed effect on alcohol intake, instead of an immediate behavioural reaction? Given that the stress response of the knockout animals is reduced, why does the absence of CRH1 increase their susceptibility to stress-induced alcohol intake, instead of decreasing it? More importantly, do these knockout animals constitute an ideal model of alcoholism? I'll have another drink before joining the authors to ponder these questions.
References
ORIGINAL RESEARCH PAPER
Sillaber, I. et al. Enhanced and delayed stress-induced alcohol drinking in mice lacking functional CRH1 receptors. Science 296, 931–933 (2002)
FURTHER READING
Weiss, F. & Porrino, L. J. Behavioural neurobiology of alcohol addiction: recent advances and challenges. J. Neurosci. 22, 3332–3337 (2002)
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López, J. Dipsomaniac mice?. Nat Rev Neurosci 3, 415 (2002). https://doi.org/10.1038/nrn860
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DOI: https://doi.org/10.1038/nrn860