Disrupting brain's stress centres worsens drug withdrawal symptoms
Disrupting the brain's stress response mechanism worsens drug withdrawal symptoms in mice, while a hormone called corticosterone alleviates them, according to new French-led research. The study, which was partly funded through a Marie-Curie grant from the European Union, is published in the latest edition of the journal Neuron. Dependence on opiate drugs, such as heroin, is a major public health issue in many parts of the world. According to figures from the European Monitoring Centre for Drugs and Drug Addiction (EMCDDA), most of the EU's 1.7 million problem drug users are heroin users, and over two thirds of acute drug-related deaths in the EU involve opioids. In opiate users, the high following a dose of the drug is inevitably followed by a low, featuring severe withdrawal symptoms including pain, nausea, agitation and sweats. The severity of these symptoms means that it is extremely difficult for drug addicts to give up their habit, yet current treatments fail to effectively relieve withdrawal symptoms. In this latest research, the scientists looked at the role of a molecule called corticotrophin-releasing factor (CRF) in regulating the body's response to opiate addiction and withdrawal symptoms. CRF is a receptor molecule which sits on the surface of the cell and triggers reactions in the cell when activated. As its name suggests, when activated it triggers the release of a hormone called corticotrophin, and the CRF system helps the body to cope with stressful events. The researchers created mice which lacked the gene for the CRF receptor, and gave them ever increasing doses of morphine before stopping the treatment to induce withdrawal symptoms. They found that the mice lacking CRF experienced much stronger withdrawal symptoms and suffered for longer than normal mice. They also detected genetic changes in the brains of the mice, indicating that the brain's stress response circuitry was not working properly. However, giving the mice corticosterone in their drinking water reduced the withdrawal symptoms of the mice that lacked the CRF receptor and restored the brain's stress response circuitry. 'The findings of the present study demonstrate that, like hyperactive stress systems, sever deficiencies in major components of the stress-responsive system may worsen the somatic reactions to drug withdrawal,' the researchers write.