Stress, a new study has said, can precipitate a low mood leading to relapse in cocaine seeking.
The research team from University of Washington (UW) has shown that stress evoked changes in circuits, which regulated serotonin in certain parts of the brain that precipitates a low mood and a relapse in cocaine-seeking.
"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).
"Stress appears to be a motivator for the relapse in drug seeking," said researcher Dr. Benjamin Land, a former UW doctoral student now in the Department of Psychiatry at Yale University.
"They feel crummy so they go where there might be something that will make them feel okay again," Land added.
They head to a spot that had the drug available in the past, an action researchers call cocaine place preference.
It is believed that drug seeking is regulated by dopamine, a chemical nerve signal associated with motivating and rewarding behaviour.
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, a chemical nerve signal that has been associated with wake and sleep cycles, mood, anger, status and aggression, 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.
The researchers revealed 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 during a troubling experience.
Research suggests that this response is mediated by the stress-evoked release of dynorphins, the "feel bad" brain signals.
Scientists had previously proposed that an activated dynorphin/kappa opioid receptor system stopped the release of dopamine and thereby made the mice feel miserable enough to cause aversions.
When scientists inactivated the kappa opioid receptors involved in the serotonin system they were able to block both the aversive responses and the stress-induced reinstatement of cocaine-place preference.
The study appears in Proceedings of the National Academy of Sciences.