Animal Models of Vulnerability to Addiction

Vulnerability to Addiction

Another approach to investigating individual differences in the vulnerability to addiction has been to characterize individual animals in terms of their propensity to show responses that relate to the DSM-IV (now DSM-5) criteria for addiction. Three domains have been identified from the DSM-5 criteria that can be linked to animals models:

FIGURE 3.14 Acquisition of amphetamine self-administration of rats in high-responder and low-responder groups after repeated intraperitoneal administration of saline. After saline treatment, the groups (n = 10 per group) differed in their acquisition of self-administration both in terms of total amphetamine administered over the five days and in terms of the number of injections over the different days. [Taken with permission from Piazza PV, Deminiere JM, Le Moal M, Simon H. Factors that predict individual vulnerability to amphetamine self-administration. Science, 1989, (245), 1511–1513.]

i) Difficulty stopping or limiting drug use (items 3–4 in the DSM-IV),

ii) High motivation to seek and use the drug (items 5–6 in the DSM-IV), and

iii) Maintenance of drug use despite negative consequences (item 7 in the DSM-IV).

Using these three diagnostic domains, studies of intravenous cocaine self-administration in Sprague-Dawley rats have shown that the severity of cocaine use can be assessed in three animal models that represent these diagnostic domains:

i) Drug seeking during periods when drug is not available,

ii) Breakpoints on a progressive-ratio schedule of reinforcement, and

iii) Persistence of self-administration despite punishment.

Using such criteria, a certain percentage of animals can be ranked according to addiction-like behavior, and an “addiction score” can be computed, from 0 (no addiction-like behavior) to 3 (high addiction-like behavior; Deroche-Gamonet et al., 2004; Belin et al., 2008). Animals with a score of 3 escalate drug intake more rapidly and to a much larger extent than animals with lower scores. They also show greater responses to contextual and drug-associated cues and exhibit much more reinstatement. This model is reliable and based on the link to DSM-IV and DSM-5 criteria. It also has some significant predictive validity.

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