Mood disorder can increase an individual's risk for substance abuse, but there is evidence that the converse is true; substance abuse can lead individuals to stress-related illnesses.

A new study finds that repeated cocaine use increases the severity of depressive-like responses in a mouse models. Researchers were able to identify mechanism that shows vulnerability due to cocaine use. The research is published by Cell Press issue of the Journal Neuron.

The new find may direct development of new treatments for mood disorders associated with substance abuse.

"Clinical evidence shows that substance abuse can increase an individual's risk for a mood disorder," explains senior study author, Dr. Eric Nestler from Mount Sinai School of Medicine "However, although this is presumably mediated by drug-induced neural adaptations that alter subsequent responses to stress, the mechanisms underlying this phenomenon were largely unexplored."

Researchers examined whether histone H3 lysine 9 dimenthylation (H3K9me2), a prominent type of chromatin modification, might be involved in the effects of repeated cocaine use on vulnerability to depressive-like behaviors.

Histones are found in the nucleus of cells, reduction in levels reflects a decrease in the number of histone methyl groups, which have been linked to mood disorders.

Researchers found that cocaine increases the susceptibility of mice to stress in a well-established model of depression and that decreased H3K9me2 in the nucleus accumbens, a major reward center in the brain.

"Our results provide fundamentally novel insight into how prior exposure to a drug of abuse enhances vulnerability to depression and other stress-related disorders," concludes Dr. Nestler. "Identifying such common regulatory mechanisms may aid in the development of new therapies for addiction and depression."