New clue to how drug addiction works in the brain
10 May 2006
A team of scientists, led by Dr Andrew Lawrence at the Medical Research Council (MRC) Cognition and Brain Sciences Unit in Cambridge, investigating a rare behavioural disorder associated with the treatment of Parkinson’s disease, has discovered new evidence that is helping MRC researchers understand the brain mechanisms behind drug addiction, published this month in the Annals of Neurology. The full article is available to read (PDF 233k)
One highly effective treatment for the motor disability of Parkinson’s disease is known as dopaminergic drug therapy. However, some of the drugs used, known as antiparkinsonian dopaminergic medications, share some of the stimulant properties of commonly abused drugs such as amphetamine and cocaine. These have the potential to be compulsively used by a small group of susceptible individuals with Parkinson’s disease, causing harmful social, psychological, and physical effects. Patients with this condition, termed “dopamine dysregulation syndrome”, meet clinical criteria for substance dependence and addiction. They frequently also show behavioural compulsions, such as compulsive gambling, eating and hyper-sexuality.
Researchers at the MRC Cognition & Brain Sciences Unit, the MRC Clinical Sciences Centre and the National Hospital in London examined the brain alterations linked to this condition, using a brain imaging technique called positron emission tomography (PET). They looked at changes in brain dopamine release following a dose of medication in patients with dopamine dysregulation syndrome, compared with a control group of patients also treated with the drug, but not showing signs of substance dependence.
Patients with dopamine dysregulation syndrome showed greatly enhanced drug-induced release of brain dopamine in one brain region, the ventral striatum, which is known to play a role in the motivating properties of natural rewards such as food and sex, compared with control patients. Furthermore, those individuals who showed the greatest craving for the drug showed the greatest levels of dopamine release. In addition, patients with dopamine dysregulation showed increased levels of a personality trait linked to risk taking and showed enhanced motivation for money reward as well as drug reward.
Dr Lawrence said, “This study provides compelling clinical evidence that drugs of abuse work by ‘hijacking’ brain structures involved in natural reward, especially in vulnerable individuals. The findings are also relevant to our understanding of behavioural addictions, such as compulsive gambling. The study of dopamine dysregulation syndrome in Parkinson’s disease is a valuable clinical paradigm in which to study mechanisms of compulsive drug use. It may provide important insights into compulsive behaviours in general, which impact greatly on society as a whole.”
These findings are published as:
Evans AH, Pavese N, Lawrence AD, Tai YF, Appel S, Doder M, Brooks DJ, Lees AJ, Piccini P. Compulsive drug use linked to sensitized ventral striatal dopamine transmission.
Ann Neurol. Vol 59 No 5 May 06
See also:
Lawrence AD, Evans AH, Lees AJ. Compulsive use of dopamine replacement therapy in Parkinson's disease: reward systems gone awry? Lancet Neurol. 2003 Oct;2(10):595-604.
