The addicted brain

Breaking ground in understanding the neurochemical and molecular aspects of addiction

Heavy ecstasy use is linked to an increase in depressive symptoms in certain people with a specific genetic predisposition

Drug addiction research has made phenomenal advances over the last couple of decades. The initial molecular sites of action of virtually all the major drugs of abuse, including cocaine, heroin, amphetamine, nicotine and alcohol have been identified. The main components of a ‘reward system’, and how it connects to brain areas involved in motivation and emotion, are now defined, and much has been discovered about the chemical messenger systems such as dopamine and noradrenaline that are fundamental to the mechanism of addiction.

Many of these advances have depended on research carried out in Cambridge. Cambridge neuroscientists characterised the important re-uptake mechanism for noradrenaline neurons that is blocked by drugs such as cocaine and amphetamine. Identifying that dopamine release in an area of the brain called the nucleus accumbens is responsible for amphetamine's stimulant behavioural effects was also a Cambridge discovery. Investigators at Cambridge are continuing to contribute importantly to the characterisation of the dopamine nerve cells central to the reward system, including some recent discoveries regarding the role of dopamine in incentive-motivation and learning. Collaborations with researchers at the Clinical School led to the striking finding that dysregulation of dopamine in the nucleus accumbens is responsible for the behavioural changes that many patients with Parkinson's disease experience, such as sudden compulsive gambling. The theory that drug addiction is a form of aberrant learning resulting from a ‘hijacking’ of the natural reward system, has also depended considerably on the work of Cambridge researchers. Furthermore, researchers from the University Department of Psychiatry recently showed that heavy ecstasy use is linked to an increase in depressive symptoms in certain people with a specific genetic predisposition.

Scientists are using knowledge of the neurochemical aspects of addiction to develop new pharmaceutical treatments for addiction, with one compound already in clinical trials

Current work at the Behavioural & Clinical Neuroscience Institute in Cambridge is focusing on whether drug addiction may entail a form of habit learning controlled by the dorsal striatum, a brain structure related to the nucleus accumbens. One of the predictions is that drug cravings arise in part from memories for cues that have become associated with the drug. By focusing on the neural basis of these memories, Cambridge neuroscientists hope selectively to disrupt their formation and break the drug-addiction cycle. This has enormous therapeutic potential for the treatment of drug addiction. In addition, multidisciplinary teams of researchers are engaged in identifying those factors, including genetic ones that predict whether someone is vulnerable to the effects of drugs of abuse. The consequences of chronic drug abuse and its harmful effects on mental performance and brain activity are being studied in drug addicts from the Cambridge region using sophisticated imaging techniques. Importantly, Cambridge scientists are utilising knowledge about the neurochemical and molecular aspects of addiction to help develop and evaluate new pharmaceutical treatments for addiction, with one such compound already in clinical trials.

In complementary work, researchers in the Department of Pharmacology have been investigating how stress can have a major impact on addiction. Researchers are investigating how neuropeptide and hormonal mediators of stress response interact with dopamine signalling in the nucleus accumbens and related structures to modulate cocaine-induced long-term behavioural changes.