Nerve cell molecule has antidepressant effect; animal study may lead to more effective treatments for depression

Mice lacking the molecule -- known as Cdk5 -- exhibited the same behaviors seen in mice given antidepressant drugs.

"We immediately realized that these mice could teach us something important about depression and that we could use them to study new pathways that might serve as targets to treat the disease," said senior author James Bibb, PhD, of the University of Texas Southwestern Medical Center, who directed the study.

When dopamine and serotonin, brain chemicals involved in mood regulation, act at brain cells, a "wave" of the signaling molecule cyclic adenosine monophosphate (cyclic AMP) is generated. Normally, another molecule, phosphodiesterase, breaks down the cyclic AMP. However, Bibb and his colleagues discovered that phosphodiesterase did not do its job -- the wave of cyclic AMP did not stop -- in mice that lacked Cdk5. Without Cdk5, the mice behaved with more resilience to stress and showed strong antidepressant-like behavior. The discovery that Cdk5 regulates phosphodiesterases opens up new opportunities to target them.

"Our hope is that the conceptual advances these findings represent will contribute to the development of new depression therapeutics," Bibb said.

Research was supported by the National Institute of Mental Health, the National Institute on Drug Addiction, and the Department of Psychiatry at the University of Texas Southwestern Medical Center.