Low Dose Amphetamine Exposure in Adolescence Cross Sensitizes Adult Mice to Methamphetamine

Abstract

Amphetamine (AMPH) is a central nervous system stimulant and an effective treatment for ADHD among adolescents, in the form of Adderall®. The rise in the number of diagnoses of this disorder, however, comes with an increase in the possibility of wrongful AMPH prescription as well as an increased prevalence of AMPH abuse. Behavioral sensitization is a heightened behavioral response to a drug after repeated exposure, and it is a behavioral expression of neurological changes. These neurological changes are important in current models of addiction, so behavioral cross-sensitization with similarly acting drugs (e.g., methamphetamine (METH)) is useful as a measure of addiction. A previous study in this lab exposed adolescent mice to either a 1.0 mg/kg or a 10 mg/kg dose of AMPH during adolescence and tested for cross-sensitization to METH in adulthood. Considering that 1.0 mg/kg is at the higher end of a therapeutic AMPH dose, the current study examines more clinically relevant doses. In this study, male and female C57B1/6J mice were injected with either 0.01 mg/kg, 0.1 mg/kg, or 1 mg/kg of dextro-AMPH (Sigma-Aldrich, St. Louis, MO) or with saline for ten days during adolescence beginning on postnatal (P) day 22. Dextro-AMPH is one of the forms of AMPH found in Adderall®. On P90, they began testing in an open field chamber (OFC; Kinder Scientific, Poway, CA). Each experiment began with acclimation to the testing environment over 30min (i.e., habituation) followed by either a sub-acute (0.5mg/kg), i.p. challenge dose of METH (Sigma) or saline and a 70min OFC test session. Mice that were exposed to either the 0.1 mg/kg or the 1.0 mg/kg dose of AMPH during adolescence demonstrated increased sensitization to the sub-acute dose of METH in adulthood while the mice exposed to saline had no such response. Male mice also demonstrated increased sensitization when compared to females, but only at the 1.0 mg/kg AMPH dose.