Research links nicotine receptors to depression



A Yale researcher was recently awarded a two-year, $100,000 grant for cheering up mice, but her research could bring similar effects to humans, too.

The National Alliance for Research on Schizophrenia and Depression presented the grant to Marina Picciotto for her work concerning the relationship between nicotine receptors in the brain and antidepressants.

Picciotto, associate professor of psychiatry, neurobiology and pharmacology at the Yale School of Medicine, received the Independent Investigator grant for innovative research after her laboratory demonstrated that the inhibition of nAChRs, nicotinic acetlycholine receptors, in the brain contributed to the therapeutic effects of the antidepressant amitriptyline.

“[Picciotto’s] results provide the first evidence that antagonism of nAChRs may be important for the therapeutic actions of antidepressants,” according to NARSAD’s website. “These studies will contribute to the validation of nicotonic receptors as novel targets for antidepressant development.”

According to Picciotto, this finding is clinically important because approximately 30 percent of Americans who suffer from depression do not respond to current medications. Picciotto’s investigation into the relationship between nicotine receptor blockers and antidepressants could benefit patients who do fully respond to classical antidepressants, she said.

Picciotto’s interest in the relationship between nicotine and antidepressants was triggered by reports that many individuals smoke to “medicate” their mood and that smokers often experience their first episodes of severe depression after quitting. Picciotto and her lab tested the emerging hypothesis that blocking nicotine receptors in the brain assists the performance of antidepressants.

They induced depression in mice, which were then treated with either the antidepressant amitriptyline or a nicotine receptor blocker for three to four weeks.

“When the classical antidepressant and nicotine receptor blockers were compared, they seemed to produce the same affect,” Picciotto said.

In addition, when augmented with a nicotine receptor blocker, the short term administration of an antidepressant also improved the behavior of the mice, said Picciotto.

Picciotto’s lab then engineered mice without nicotine receptors and found that these mice did not respond to either the antidepressant or nicotine receptor blockers.

These findings led Picciotto to conclude that blocking nicotine receptors can enhance the action of a classical antidepressant and that nicotine receptors are required in order to respond to an antidepressant.

Tony George, associate professor of psychiatry at Yale, is currently conducting a clinical trial that is independent of but related to Picciotto’s study.

“My study is a human trial in depressed patients treated with SSRI antidepressants and augmented with the nicotinic antagonist mecamyalmine [versus placebo],” George said.

According to Picciotto, George’s work represents the practical side of her basic science research and is indicative of the effects further research on this subject may have on patients suffering from depression.

With an Independent Investigator grant that began Oct. 1, Picciotto hopes to extend her research in three directions.

“We want to know how general this phenomenon is, we want to extend [our testing] to other antidepressants, [and] we want to know what’s going on at the molecular level,” Picciotto said.

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