Brain's nicotine receptors also target for anti-depressants

November 16, 2004

New Haven, Conn.--The same receptors in the brain that are activated when a person smokes cigarettes also play a critical role in the effectiveness of antidepressants, according to a study by Yale researchers in the November issue of Biological Psychiatry.

What this means, particularly for patients who are suicidal, is that finding a way to activate these receptors will make anti-depressants work more quickly. Most anti-depressants now take up to three weeks to bring emotional relief.

"Just the ability to block the reuptake of serotonin isn't enough, otherwise it wouldn't take two to three weeks to be effective, " said Marina Picciotto, associate professor of psychiatry, pharmacology and neurobiology at Yale School of Medicine and senior author of the study. "This finding has implications for those patients who are depressed to the point of being suicidal, and for the 30 percent of people who are not responsive to anti-depressants that are now available."

The primary pharmacologic treatment for depression over the past several decades has been drugs that inhibit synaptic reuptake of monoamine neurotransmitters. Recent evidence indicates other neurotransmitter systems might play a role in the mechanism of action of antidepressants, Picciotto said.

In this study in mice, she and her colleagues tested the action of antidepressants with and without mecamylamine, a noncompetitive antagonist (blocker) in nicotinic acetylcholine receptors (nAChRs). In a separate study using knockout mice that lack these receptors, they found that the function of the nicotine receptor in the brain was an essential component of the therapeutic action of antidepressants.

Picciotto said the next step will be to study the role of nAChRs in regulating the behavioral and cellular responses to antidepressants. They will see if there is a direct effect mediated by nAChRs or an indirect effect of modulating neurotransmission in other cell types. "Use of more specific nAChRs antagonists, both alone and in combination with classic antidepressants, could lead to the development of novel and more effective treatments for individuals who suffer from depression," she said.
-end-
Citation: Biological Psychiatry, Vol. 56 (9); pp 657-664.

Yale University

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