Are adolescents more vulnerable to drug addiction than adults? Evidence from animal models

Abstract

Background and rationale: Epidemiological evidence suggests that people who begin experimenting with drugs of abuse during early adolescence are more likely to develop substance use disorders (SUDs), but this correlation does not guarantee causation. Animal models, in which age of onset can be tightly controlled, offer a platform for testing causality. Many animal models address drug effects that might promote or discourage drug intake and drug-induced neuroplasticity.

Methods: We have reviewed the preclinical literature to investigate whether adolescent rodents are differentially sensitive to rewarding, reinforcing, aversive, locomotor, and withdrawal-induced effects of drugs of abuse.

Results and conclusions: The rodent model literature consistently suggests that the balance of rewarding and aversive effects of drugs of abuse is tipped toward reward in adolescence. However, increased reward does not consistently lead to increased voluntary intake: age effects on voluntary intake are drug and method specific. On the other hand, adolescents are consistently less sensitive to withdrawal effects, which could protect against compulsive drug seeking. Studies examining neuronal function have revealed several age-related effects but have yet to link these effects to vulnerability to SUDs. Taken together, the findings suggest factors which may promote recreational drug use in adolescents, but evidence relating to pathological drug-seeking behavior is lacking. A call is made for future studies to address this gap using behavioral models of pathological drug seeking and for neurobiologic studies to more directly link age effects to SUD vulnerability.

Fig. 1

Percentages of the US population over the age of 12 years who have ever tried the indicated drug (top number, light gray circle); who used the indicated drug in the past month (middle number, darker gray circle); who meet criteria for dependence on the indicated drug (bottom number, black circle). Numbers in the center of each diagram represent the percentage of people who have ever tried the indicated substance who are currently dependent. Data obtained from the NSDUH 2007, lifetime use, past month use, DSM-IV dependence criteria (for all drugs except tobacco), and daily cigarette use (for tobacco)

Fig. 2

Stages in the progression to drug dependence (rectangles) and animal models related to each stage (ovals; self-admin, self-administration)