Animal Models of Addiction

Validation of Animal Models of Drug Addiction

Animal models are critical for understanding the neuropharmacological mechanisms involved in the development of addiction. As mentioned above, no animal model fully emulates the complete addiction process, but several models do reflect many elements of the syndrome. An animal model can be viewed as an experimental protocol that is used to study a given phenomenon found in humans.

Construct validity refers to the interpretability, “meaningfulness,” or explanatory power of a model and incorporates most other measures of validity, in which multiple measures or dimensions are associated with conditions known to affect the construct. This is the most relevant conceptualization of validity for animal models of addiction (Ebel, 1961). An alternative conceptualization of construct validity is the requirement that the model must be functionally equivalent, defined as “assessing how controlling variables influence outcome in the model and the target disorders” (Katz and Higgins, 2003). The most efficient process for evaluating functional equivalence is through common experimental manipulations that should have similar effects in the animal model and the target condition. This process is very similar to the construct predictive validity (see below).

Face validity is often the starting point in animal models in which animal syndromes are produced that resemble those found in humans to study specific parts of the human syndrome (McKinney, 1988). For example, rats that intravenously self-administer drugs of abuse show patterns of responding that are identical to those of humans.

Reliability refers to the stability of the model and the consistency with which the dependent variable can be measured. Reliability is said to be achieved when small within- and between-subject variability is found after repeated measurements of the variable, and the phenomenon is readily reproduced under similar circumstances (Geyer and Markou, 2002).

Predictive validity refers to the model’s ability to lead to accurate predictions about the human phenomenon based on the animal’s response within the model. This type of validity is used most often in animal models of psychiatric disorders to refer to the ability of the model to identify pharmacological agents with potential therapeutic value in humans. However, when predictive validity is more broadly extended to understanding the physiological mechanisms of action of psychiatric disorders, it can incorporate other types of validity – etiological, convergent, concurrent, or discriminant – that are also considered important for the model.

The present section describes various animal models that have been shown to be reliable, and in many cases to have construct validity for the various stages of the addiction process, including binge/intoxication, withdrawal/negative affect, and preoccupation/anticipation.

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