Animal Models in Addiction Research

Animal Models in Addiction Research

Many of the recent advances in addiction research have been made possible by the use of animal models. Since drugs of abuse are not only rewarding but also reinforcing, an animal will learn a behavior (eg, press a lever) when paired with drug administration. In such a self-administration paradigm, the number of times an animal is willing to press the lever in order to obtain a single dose reflects the strength of reinforcement and is therefore a measure of the rewarding properties of a drug. Observing withdrawal signs specific for rodents (eg, escape jumps or “wet-dog” shakes after abrupt termination of chronic morphine administration) allows the quantification of dependence. Behavioral tests for addiction in the rodent have proven difficult to develop, and so far no test fully captures the complexity of the disease. However it is possible to model core components of addiction, for example by monitoring behav-ioral sensitization and conditioned place preference. In the first test, an increase in locomotor activity is observed with intermittent drug exposure. The latter tests for the preference of a particular environment associated with drug exposure by measuring the time an animal spends in the compartment where a drug was received compared with the compartment where only saline was injected (conditioned place preference). Both tests have in common that they are sensitive to cue-conditioned effects of addictive drugs. Subsequent exposures to the environment without the drug lead to extinction of the place preference, which can be reinstated with a low dose of the drug or the presentation of a conditioned stimulus. These persistent changes serve as a model of relapse and have been linked to synaptic plasticity of excitatory transmission in the ventral tegmental area, nucleus accumbens and prefrontal cortex (see also Box: The Dopamine Hypothesis of Addiction). Recent findings suggest that prolonged self-administration of cocaine leads to behaviors in rats that closely resemble human addiction. Such “addicted rats” are very strongly motivated to seek cocaine, continue looking for the drug even when no longer available, and self-administer cocaine in spite of nega-tive consequences, such as an electric foot shock. These find-ings suggest that addiction is a disease that does not respect species boundaries.