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Suppressing Satisfaction: GLP-1’s Potential in the Treatment of Addiction

By Ian MacArthur

Consuming a meal when hungry is often accompanied by a profound sense of satisfaction. This state of feeling full and satisfied is induced by the release of glucagon-like peptide-1 (GLP-1), a hormone that binds to receptors when a particular craving is quenched. Now, researchers believe that GLP-1 and other compounds that mimic its effects can be used in the treatment of tobacco addiction. By blocking the receptors involved in gratification, GLP-1 and similar molecules might reduce the satisfaction obtained from smoking and aid in reducing nicotine dependence.

What GLP-1 looks like structurally. This is the hormone in our bodies that lets us know when we’re satisfied with a meal. (via Wikipedia)

To demonstrate the regulatory effect of GLP-1 on satisfaction, scientists at the University of Gothenburg in Sweden performed studies on mice that had been given doses of nicotine. The nicotine induced an increase in activity as evidenced by the mice’s movement patterns. Some mice were then given a dose of Exendin-4 (Ex4), a compound that mimics GLP-1’s interaction with receptors. It was observed that the mice treated with Ex4 were afterwards less active and displayed lower levels of dopamine compared to the untreated mice.  From this the researchers concluded that Ex4 had reduced the reward associated with nicotine consumption. Another important result of the study was that no decrease in activity was observed in mice that hadn’t been given nicotine before Ex4 treatment. This suggests that GLP-1 and related compounds only reduces satisfaction associated with particular activities, such as nicotine and food consumption, but does not affect normal behavior.

The scientists believe that drugs designed to mimic GLP-1 and Ex4 in their effects on gratification can be used to help treat nicotine and other addictions. Analogous studies performed on mice that had been given alcohol, cocaine, and amphetamines produced similar results. By inhibiting the sense of reward produced by ingesting these substances, these drugs could help addicts kick the worst of habits.

While these studies show the potential for drugs that mimic the behavior of GLP-1 to treat addiction, their effect on behavior as a whole must be cautiously investigated. An obvious danger of using such drugs would be the suppression of gratification produced by behaviors other than the ones that are desirable to suppress. GLP-1 is not specifically associated with nicotine and substance-induced gratification, so the potential for an analogous drug to affect gratification associated with other activities, such as exercise and creative endeavors, is very high.

As previously mentioned, no reduction in activity or dopamine levels were observed in mice that had not been given nicotine before being treated with Ex4. While this seems to indicate that the compound does not affect normal behavior, the qualifications of this claim, based solely on dopamine and motor activity, are quite narrow. Until further studies are performed to identify how these compounds affect behavioral brain chemistry in a more comprehensive way, their potential use as treatments for addiction should be taken lightly.

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