High Impulsivity Predicts The Switch To Compulsive Cocaine-taking

Scientists at the University of Cambridge have found impulsivity, a trait often associated with addicts’ behaviour, predicts whether casual drug use will lead to compulsive drug use. Their findings were recently reported in Science.

Many individuals take addictive drugs at some point in their lives – not just illicit drugs like cocaine and heroin, but also legal and commonly available substances such as alcohol and nicotine. But only a sub-group of those who take drugs eventually lose control over their drug use and become ‘addicted’.

These individuals take more drugs than intended, seek and take drugs compulsively and persist in doing so despite the many adverse consequences, such as compromising their health, family relationships, friendships and work. Many resort to criminal behaviour to obtain the funds necessary to sustain their compulsive drug use.

Why are some individuals vulnerable to this transition from casual to compulsive drug use? Scientists have concluded that there is a genetic vulnerability to addiction, which is best known for alcoholism. However, the precise relationship between vulnerability genes and addictive behaviour remains to be established.

Drug addicts are often described as being impulsive, risk-taking or sensation-seeking and make poor choices (for example, taking drugs in the present whilst nevertheless being aware that this is a ‘bad choice’ because of the damaging consequences in the future).

Professor Barry Everitt said: “It has never been clear whether these behavioural characteristics are a cause or a consequence of their long-term abuse of drugs. This is where animal studies have unique power, because they can probe causal relationships in a way that is impossible and unethical in human populations.”

The Cambridge research team, which included Professor Everitt, Drs David Belin, Adam Mar, Jeff Dalley and Professor Trevor Robbins working in the Departments of Experimental Psychology and Psychiatry within the Behavioural and Clinical Neuroscience Institute, showed that a spontaneously occurring tendency, or ‘trait’, of impulsivity in rats predicts the transition from casual to compulsive drug use and drug addiction.

Using animal models developed by the research group, the researchers established groups of rats showing high or low impulsivity (highly impulsive rats were those that had more difficulty in waiting to sample predictive environmental cues before responding) as well as groups that showed high or low responses to novelty stress (a model of sensation seeking).

The different groups of rats were then allowed to self-administer cocaine. Whilst novelty seekers were initially more sensitive to the positive effects of cocaine, they did not go on to display compulsive drug seeking. In contrast, highly impulsive subjects when given long-term access to cocaine, developed compulsive cocaine use and other characteristics of drug addiction.

Professor Everitt stated: “This study is important because it shows that impulsivity is a vulnerability characteristic that predicts a switch to compulsive drug use when individuals are exposed to and take cocaine. Therefore, drug addiction is characterized by a shift from impulsive to compulsive behaviour.

“The study also shows that initial responsiveness to the positive effects of cocaine seen in sensation seekers does not predict the development of addiction.”

Professor Everitt’s team is now poised to identify the neurobiological basis of the impulsive characteristic and to investigate its possibly genetic origins. In research published a year ago by Dr Dalley and colleagues, also in Science, it was shown that highly impulsive rats have low levels of a particular type of dopamine receptor — the D2/3 receptor — specifically in a part of the forebrain called the nucleus accumbens, which has long been associated with the addiction-promoting effects of addictive drugs. They also showed that highly impulsive animals escalated their cocaine intake to a far greater extent than non-impulsive animals when given free access to the drug.

The new study represents a major advance by showing that these neural and behavioural changes are forerunners of the eventual transition to drug addiction. The results also suggest that impulsive behaviour is a promising focus for future behavioural and pharmacological treatments for addiction and, perhaps especially, for preventing relapse to a drug taking habit in those attempting to relinquish it and abstain.

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New approaches to cocaine addiction
The molecular signature of cocaine addiction

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