Stress-evoked changes in circuits that regulate serotonin in certain parts of the brain can precipitate a low mood and a relapse in cocaine-seeking, based on mouse studies published online this week in the Proceedings of the National Academy of Sciences.
"The impetus for this research was our interest in how stress alters the brain's cell receptors and protein signals in ways that lead to mood changes, depression, anxiety, and drug seeking," said Dr. Michael Bruchas, acting instructor of pharmacology at the University of Washington (UW), who with Dr. Benjamin Land, a former UW doctoral student now in the Department of Psychiatry at Yale University, co-led the recent study of the adverse effects of stress-activated brain pathways. The senior author was Dr. Charles Chavkin, the Allan and Phyllis Treuer Professor of Pharmacology and director of the UW Center for Drug Addiction Research
A common belief is that drug seeking is regulated by dopamine, a chemical nerve signal associated with motivating and rewarding behavior. Dopamine may still have a key role, the researchers noted, which is why they were surprised to find harmful effects of stress converging in a brain region the dorsal raphe nucleus --where nerve cells that use serotonin are abundant. These nerve cells also project to other structures found on either side of the brain -- the nucleus accumbens -- which are thought to play roles in feeding and drug addiction. Serotonin is a chemical nerve signal that has been associated with wake and sleep cycles, mood, anger, status and aggression
In explaining their study, the researchers said that the dynorphin/kappa opioid system, found in certain brain cells, can be activated either through repeated stress or by giving a chemical that triggers a receptor on the cells. Activation of this system produces what is called conditioned place aversion in mice. They avoid smells, locations or tactile sensations similar to those present du
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