The relative invulnerability of juvenile rats to addiction: Longitudinal assessment of risk behaviors and their relationship to cocaine self-administration

Abstract

Individuals who initiate drug use before 14 years of age are at increased risk of developing a lifelong addiction. Risk behaviors associated with drug use in adult animals include novel reactivity, novelty preferences, and sucrose preferences. Whether those same behaviors predict drug use in young populations is not well-studied. We determined how these risk behaviors i) change across development in Sprague-Dawley male and female rats and ii) predict adolescent cocaine self-administration when risk is assessed in juveniles. A longitudinal design characterized the behavioral trajectory of rats at the ages of 21 (juvenile), 56 (adolescent), and 96 (adult) days of age. Novel reactivity and sucrose preferences increased with maturation, with females having higher reactivity levels than males. Sucrose preferences predicted increased cocaine intake in both sexes, an effect primarily driven by males. Novelty preferences, especially in males, predicted less cocaine intake. Segregation of the data into high and low tertiles (risk and resilience) revealed that high sucrose preference predicted cocaine infusions. Low levels of novel reactivity in females significantly correlated with presses on the active lever for cocaine. The number of days to acquire stable intake was the only metric to classify a group with more overall cocaine consumption. Juvenile rats are either too immature to demonstrate predictive behavior related to novelty or, alternatively, a more extreme phenotype may be necessary to identify addiction risk.