A brain region that helps us limit alcohol consumption - Printable Version
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A brain region that helps us limit alcohol consumption - mtwalsh01 - 04-03-2014
A brain region called the lateral habenula (LHb) may be vital in directing control of ethanol consumption by mediation of learning driven by the aversive effects of the drug. These are the findings of a study on laboratory rats from researchers in the University of Utah which has relevance for understanding of alcohol addiction in humans. The study was published in the journal PLoS One on April 2nd 2014.
The lateral habenula is well established as having an important role in learning driven by negative outcomes. Previous studies had indicated that the lateral habenula is implicated in negative regulation of motivation to take drugs of abuse such as cocaine and nicotine, suggesting that it drives learning from the aversive effects of these drugs. Similarly, ethanol consumption is associated with initially positive effects but ultimately aversive effects such as delayed hangover. Animal studies had previously demonstrated a link between conditioned taste aversion (CTA) and decreased ethanol consumption, suggesting a role for learning driven by aversive outcomes in reduction of ethanol consumption. This has likely clinical relevance as it is established that in humans, decreased sensitivity to the aversive effects of alcohol is more likely to result in problem drinking such as binge drinking and alcoholism.
These existing studies inspired the University of Utah scientists to examine the role of the lateral habenula in regulation of ethanol intake. They studied two groups of rats. In one group the lateral habendula was inactivated while in the other a sham procedure was performed leaving the brain region intact. The researchers studied patterns of consumption of ethanol in the two groups of rats, both in terms of voluntary consumption of ethanol provided in the rats’ cages and in a system whereby the rats could self-administer the ethanol.
The results showed that in the lesioned rats who lacked the lateral habendula, voluntary ethanol intake escalated significantly more rapidly over the course of eight weeks of observation and levelled off at a significantly higher level than in the control rats. Levels of self-administration of ethanol were also significantly higher in the lesioned rats. In an effort to determine if the removal of the lateral habendula function affected conditioned taste aversion associated with alcohol, the researchers made a desirable supersaccharin solution available to the rats for thirty minutes before immediate injection with either ethanol or saline. Conditioned taste aversion to the supersaccharin arose in both groups associated with ethanol administration, but it was lower in the lesioned rats and they also tended to recover more quickly from this conditioned taste aversion.
First co-author on the study, Andrew Haack explained the potential clinical significance of these findings: "The way I look at it is the rewarding effects of drinking alcohol compete with the aversive effects….When you take the aversive effects away, which is what we did when we inactivated the lateral habenula, the rewarding effects gain more purchase, and so it drives up drinking behavior."
This can help explain some of the physiological reasons why some people become problem drinkers as they are less sensitive to the negative effects of alcohol. The researchers think that the lateral habendula may either regulate how bad an individual feels after over-indulgence in alcohol or else regulates how effectively they learn from the adverse experience. Future studies will address these theories.
Haack AK, Sheth C, Schwager AL, Sinclair MS, Tandon S, et al. (2014) Lesions of the Lateral Habenula Increase Voluntary Ethanol Consumption and Operant Self-Administration, Block Yohimbine-Induced Reinstatement of Ethanol Seeking, and Attenuate Ethanol-Induced Conditioned Taste Aversion. PLoS ONE 9(4): e92701. doi:10.1371/journal.pone.0092701
Press release: University of Utah Health Sciences; available at http://www.eurekalert.org/pub_releases/2014-04/uouh-abr040214.php [Accessed 3 April 2014].