Rats as well as humans can become addicted to drugs

Aug 13 2004

The voluntary consumption of drugs is a behavior found in a number of species of animal. But until now it was thought that drug-addiction was a specific behavior of humans.

New research released by INSERM, the French Institute of Health and Medical Research today, shows that the behaviors which define drug-addiction in humans, can also appear in the rat when cocaine is consumed.

Drug-addiction in humans and rodents presents astonishing similarities. The discovery of drug dependence in the rat strongly suggests that drug-addiction is a true disease of the brain. These new findings should make it possible to better understand the biology of drug-addiction and improve treatments. The study is published in the current issue of Science Review.

The principal objective of any researcher who studies drug dependency is to understand the mechanisms that lead to addiction. Addiction is not classed as simply drug-taking but prolonged compulsive consumption in spite of the consequences. Compulsive consumption of drugs or addiction generally only occurs in 15-20% of the overall human drug using population and has the characteristics of a chronic disease, since the rate of relapse, even after prolonged periods of abstinence, is always very high (approximately 90%).

Until now, no true model existed for drug addiction in animals, limiting the understanding of drug dependence.

This is why the Inserm team wanted to test if drug addiction could be observed in rodents. The researchers studied the voluntary consumption of cocaine in 100 rats. The rats, free to move, consumed cocaine by inserting their muzzles into a hole in one of the walls of their "experimental room".

The animals were studied in this environment for three months. This period is a substantial portion of a rats life as average life expectancy is only two years.

Three behaviors were specifically watched for. These behaviors are considered to be standard diagnostic tests for drug dependency in humans.

• difficulty in stopping or limiting drug consumption. This behavior was tested by evaluating the requests by the rat for more cocaine. The rats had 15 minutes of no cocaine access followed by 40 minutes where cocaine was available.
• the motivation of the rat to acquire more cocaine. This behavior was tested by estimating the work that the animal was prepared to do to obtain more cocaine. The rats performed specific tasks to receive an injection of cocaine.
• consumption continues in spite of the harmful consequences. This behavior was evaluated by testing the persistence of the rat to obtain more cocaine, whilst receiving a punishment in the process.

The team then tested the propensity to "relapse". To do this the researchers exposed the rats to cocaine after periods of abstinence (5 and 30 days) and analyzed their behavior when searching for more cocaine.

The results of this study showed that rodents and man both develop addiction gradually. After one month of drug consumption no rat showed signs of drug-addiction. However, between the second and the third month of consumption the three test criteria became evident in a number of the rats. As in humans, only a limited number of "consuming" rats developed addiction behaviors (17% for the rat, 15 % for humans).

The "dependent" rats did not manage to limit their drug consumption, showing an extraordinarily high motivation for cocaine whilst continuing to receive punishments when catching the cocaine.

These results showed surprising similarities between man and rodent. The team suggests that "drug-addiction" is not simply a fact of prolonged drug exposure. It can also result from vulnerabilities in each individual to addiction. Whilst all of the animals strictly consumed the same amount of cocaine, only a small proportion developed dependency.

"Our results make it possible to propose a unified vision of the origin of dependency which is based on the interaction between the level of exposure to drugs and the degree of individual vulnerability. Drug-addiction, thus appears to have an identical status as any other disease of the brain which results most often from an interaction between a pathogenic stimulus environment and a ground of predisposition "

http://www.inserm.fr/