Animal Models of Vulnerability to Addiction
Acquisition of Drug Seeking
Models of the vulnerability to addiction have historically involved acquisition studies, in which subjects that are naive to a particular drug learn a simple operant response to obtain an intravenous delivery of the drug in a limited-access situation. Individual differences in the response to psychostimulants and other drugs of abuse in general have been widely demonstrated in humans and laboratory animals. Although the importance of individual differences in humans is well accepted in clinical practice, it has generally been neglected in animal studies. One of most sensitive models for testing the vulnerability to drugs of abuse is to provide naive animals with very low doses of drugs in an acquisition paradigm, such that only the more sensitive individuals develop self-administration. The differences are hypothesized to reflect the differential reactivity of specific neurotransmitters (Figure 3.14). Such types of differential responses have been shown for cocaine, amphetamine, and heroin. The difference between animals within a group can be further exaggerated by dividing the group in half or by the median (i.e., 50%–50%) or to maximize the phenotypic differences by comparing the lowest and highest interquartiles. Such models lead to at least two avenues of research:
i) Investigating the biological and brain parameters that differentiate behavioral phenotypes, and
ii) Characterizing the vulnerable vs. resistant phenotypes, so that the knowledge or the measure of a behavioral characteristic predicts the type of response to the drug.
These models have face validity because vulnerable subjects have a higher chance of developing addiction-like behavior, independent of the quantity of drug available (which appears to occur in the real, human world).