Depression and similar mental disorders like bi-polar disorder, anxiety, and obsessive–compulsive disorder are associated with imbalances in neurotransmitters in the brain. Neurotransmitters are signaling molecules exchanged between neurons (nerve cells) for communication purposes. One of these neurotransmitters is serotonin, and drugs that increase serotonin levels in the brain are the most widely used treatments for depression and similar conditions. Nevertheless, these drugs are not unproblematic as many patients get frustrated as it can take several weeks after taking them, before the drugs become effective, in some patients, the drugs work don’t work at all, and in others, the side effects of these drugs can be a huge problem.

The molecules in the brain to which serotonin binds to deliver its signal, are called serotonin receptors. There are seven families of serotonin receptors known and each family has a different function; some of them even have opposite effects. Conventional anti-depressants increase serotonin levels in all parts of the brain and make no difference which serotonin receptors are present in the areas they affect. A better understanding which serotonin receptor is responsible for anti-depressive and anxiety-reducing effects of serotonin could lead to the development of medications that specifically target these receptors and therefore reduce side effects and increase efficacy of the treatment compared to the current “shot-gun” approach.

In a recent publication in the journal Proceedings of the National Academy of Science (PNAS), scientists have come one step closer to this ideal. They showed that increasing the activity of the serotonin receptor 5HT1A leads to a decrease of behavior in mice that is linked to depression and anxiety. 5HT1A is a member of the 5HT1-family of serotonin receptors that is located on the cell surface of certain neurons (nerve cells) that receive serotonin signals. The signal is transmitted into the neuron by another molecule, called a G-protein which is hooked to the 5HT1A-receptor on the inside of the cell membrane. The activity of this G-protein can be turned down by another protein called a regulator of G-protein signaling (RGS).

In the publication, the researchers reported about mice in which the RGS cannot turn down the G-protein’s activity due to a mutation in the G-protein. These mice showed behaviors without being given any drugs that are usually seen when antidepressants are given to mice. These mice also reacted much stronger when they were given serotonin-increasing antidepressants when compared to control mice that did not have the mutation. These finding show that the RGS protein plays an important part in decreasing the anti-depressant effect of the 5HT1A receptor. A future medication that selectively inhibits the action of the RGS protein might be a more effective treatment for depression and related conditions, with the risk of fewer side effects compared to the current unspecific serotonin-enhancing drugs.

Reference

Talbot JN, Jutkiewicz EM, Graves SM, Clemans CF, Nicol MR, Mortensen RM, Huang X, Neubig RR, & Traynor JR (2010). RGS inhibition at G(alpha)i2 selectively potentiates 5-HT1A-mediated antidepressant effects. Proceedings of the National Academy of Sciences of the United States of America, 107 (24), 11086-91 PMID: 20534514