Adult and adolescent sensitivity to amphetamine following early treatment with methotrexate in mice

Stimulants such as amphetamine (AMPH) are a popular medication for the cognitive late effects of childhood cancer treatment. While the reinforcing properties of AMPH are well documented, little is known about these effects in childhood cancer survivors. In this study, conditioned place preference (CPP) was used to compare the reinforcing properties of AMPH among adult (PND 60) and adolescent (PND 35) mice. Within the adolescent group, mice were treated with either saline or methotrexate (0.05, 0.1, or 0.25 mg/kg) at PND 14, 15, and 16. On Day 1 of CPP, mice were given free access to a three‐compartment chamber. The non‐preferred side was paired with a dose of AMPH (1, 2, or 4 mg/kg) and the preferred side was paired with saline for 6 alternating days. On Day 8, mice were given free access to the entire chamber for 15 min, and time spent in each compartment was recorded. Adult mice showed a greater preference for the compartment paired with 1 and 4 mg/kg, while adolescent mice previously treated with saline showed a greater preference for the side paired with 2 and 4 mg/kg. Adolescent mice previously treated with methotrexate showed a greater preference for only 2 mg/kg. Findings suggest that sensitivity to the reinforcing properties of AMPH may differ between adult and adolescent mice, and this difference may be further altered by early methotrexate treatment.