A single high dose of cocaine induces differential sensitization to specific behaviors across adolescence

Abstract

Adolescence is a critical period for drug addiction. Acute stimulant exposure elicits different behavioral responses in adolescent and adult rodents. The same biological differences that mediate age-specific behavioral responsiveness to stimulants in rodents could contribute to increased addiction vulnerability in adolescent humans. This study compared the ability of a single high dose of cocaine (40 mg/kg) to induce behavioral sensitization to a challenge dose of cocaine (10 mg/kg) 24 h later in young adolescent postnatal day 28 (PN 28), mid-adolescent (PN 42), and young adult (PN 65) male rats. Horizontal activity was resolved into ambulatory and non-ambulatory movements. An observational behavioral rating was obtained by recording specific behaviors. We examined if individual behavioral responses to novelty and cocaine correlate with sensitization in each age group. Single dose cocaine pretreatment induced behavioral sensitization to non-ambulatory horizontal activity, sniffing behaviors, and stereotypies in animals of all ages. Ambulatory sensitization was observed only in the youngest adolescents. Cocaine pretreatment caused greater increases in stereotypies in the young adolescents than in adults. The magnitude of the behavioral response to the initial cocaine treatment was positively correlated with the magnitude of sensitization in individual young adolescents. High levels of novelty-induced ambulatory activity only correlated with the magnitude of ambulatory sensitization in the youngest adolescents. We conclude that a single high dose of cocaine produces age-specific patterns of behavioral sensitization. Young adolescent rats appear to be more sensitive than adults to some of the behavioral alterations induced by a single high dose of cocaine.