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New way to reduce the effects of cocaine

Posted by Sun on July 25, 2011

Branwen Morgan                                                                                                                                                                  Monday, 25 July 2011
ABC

A new target for the treatment of drug addiction has been identified by US and Chinese scientists. Research led by Dr Zheng-Xiong Xi of the National Institute on Drug Abuse in the USA has found that activation of receptors in the brains of mice can counteract the behavioural and rewarding effects of cocaine.

There are two major cannabinoid receptor types: CB1 and CB2. CB1 receptors, which are found in large numbers in the brain activated by drugs such as marijuana. They are known to stimulate the brain’s reward system, which is why they have been the focus of addiction research. CB2 receptors are primarily located on the body’s immune cells. They are also known to be involved in pain perception.Until recently, it was thought that CB2 receptors were not present in the brain or that, if they were, it was in such low density that they were not involved in drug addiction. “Due to the limitations of the technology we weren’t able to detect low levels of CB2 receptors,” says Xi. But, six years ago, CB2 receptors were found to be present and active in the brainstem. They were subsequently detected in neurons in the brain. “This prompted us to re-examine the role of CB2 receptors in drug reward and addiction,” says Xi.”Our research suggests that, even though the levels of CB2 receptors [in the brain] are very low, they are critically involved in cocaine’s actions.” The results are published online today in Nature Neuroscience.

Rewarding behaviour

In their study, Xi and colleagues trained mice to self-administer cocaine intravenously. The researchers found that activating CB2 receptors with two different ‘agonists’ reduced drug-induced behaviour such as hyperactivity. In addition, the CB2 receptor agonists reduced the bouts and amount of drug intake in normal (wild type) mice and mice who lacked the CB1 receptors, but not those that lacked CB2 receptors. Further experiments showed the observed effects were mediated by the brain’s CB2 receptors and that the rewarding effects of cocaine were blocked. “Taken all together, the present findings, for the first time suggest that brain CB2 receptors functionally modulate the acute rewarding and locomotor-stimulating effects of cocaine in mice,” says Xi.

Battling addiction

Xi adds that several pharmaceutical companies already have CB2 agonists in preclinical trials, but that they have been developed to treat pain. “Our findings open a new field; CB2 agonists have a very high potential for treating addiction,” he says. Dr Nadia Solowij of the University of Wollongong agrees and speculates that the study will also have relevance for other drug addictions including opiates. “They found minimal side-effects by specifically targeting these cannabinoid receptors and they showed specific effects on the dopamine [reward] system,” she says. However, Solowij adds that the addiction and reward systems involve interactions between many different receptor and neurochemical systems in the brain and that more research is needed to fully understand the changes that result from CB2 activation. Xi acknowledges that “these are very early initial studies,” and adds that they will now test their compounds in other animal species, starting with the rat. He and his colleagues are also focussing on finding the mechanism by which activation of CB2 receptors inhibits dopamine release.

Source: http://www.abc.net.au/science/articles/2011/07/25/3275847.htm

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