1. Late Adolescent Exposure to Amphetamine Induces Cross-Sensitization to Methamphetamine and Susceptibility to Addiction in Adulthood

Abstract

Amphetamines (AMPH) are frequently prescribed to adolescents to treat attention deficit hyperactivity disorder (ADHD) in the form of Adderall, an AMPH salt preparation. Although recognized as an effective treatment, Adderall has elevated abuse potential. Extensive neurological maturation occurs during adolescence. Alterations in brain plasticity from prior drug exposure refers to behavioral cross-sensitization, a hallmark of addiction that can be measured through heightened locomotor activity. Sexual dimorphism is prevalent in a developing adolescent brain and abusing AMPH may induce sex-specific effects. Previous studies in our lab show a sex by drug effect in AMPH-exposed early-adolescent mice (P22-P31). We hypothesize that AMPH exposure during late adolescence will induce behavioral cross-sensitization to a subacute methamphetamine (METH) dose in adulthood with sex-specific effects. In the present study, intraperitoneal injections of AMPH (1.0 mg/kg) or an equal volume of sterile saline (P42-P51) were administered during late adolescence to male and female C57Bl/6J mice. After a period of drug abstinence, adult mice (P90) were challenged with a subacute METH dose (0.5 mg/kg) or sterile saline. Behavioral cross-sensitization was assessed by monitoring locomotion in an open field chamber. Preliminary analysis suggests AMPH-exposed mice challenged with subacute METH will have increased ambulation compared to saline controls, and that males exposed to AMPH will express increased ambulation compared to AMPH-exposed females. AMPH exposure during a critical window of development may show a treatment and sex by drug effect due to long-lasting changes in brain plasticity, which has potential clinical relevance to addiction susceptibility after adolescent ADHD use and misuse.