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. 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. In this study, male and female C57B1/6J mice will be injected with either low (0.01 mg/kg) medium (0.1 mg/kg) or high (1 mg/kg) doses of AMPH (Sigma-Aldrich, St. Louis, MO) or with saline for ten days during adolescence beginning on postnatal (P) day 22. On P90 they will begin testing in an open field chamber (OFC; Kinder Scientific, Poway, CA). Each experiment begins 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. It is expected that the mice that were exposed to AMPH during adolescence will show sensitization to the sub-acute dose of METH in adulthood while the mice exposed to saline will show no such response. It is also expected that male mice will show increased sensitization when compared to females who received the same AMPH dosage during adolescence.