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Sensitivity to the rewarding and locomotor effects of amphetamine following early treatment with methotrexate and cytarabine in adolescent mice
Author(s) -
Myers Alyssa M,
Bisen-Hersh Emily B,
Walker Ellen A
Publication year - 2012
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.26.1_supplement.661.5
Subject(s) - amphetamine , methotrexate , sensitization , saline , pharmacology , cytarabine , medicine , chemotherapy , therapeutic effect , anesthesia , dopamine , immunology
Stimulants such as amphetamine (AMPH) are popular medications for the cognitive late effects of childhood cancer treatment. While the reinforcing and stimulatory properties of AMPH are well documented, little is known about these effects in childhood cancer survivors. In this study, conditioned place preference (CPP) and locomotor activity were measured to investigate sensitivity to AMPH in adolescent (PND 35) mice following neonatal exposure to chemotherapeutic agents methotrexate (MTX) and cytarabine (Ara‐C). Mice were treated with saline, MTX (2.0 mg/kg), Ara‐C (20 mg/kg) or a combination of MTX and Ara‐C (2.0 mg/kg and+ 20 mg/kg) at PND 14, 15, and 16. At the low dose of AMPH (1 mg/kg), chemotherapy‐treated mice spent significantly more time on the AMPH‐paired side. MTX and Ara‐C treated mice showed higher activity levels compared to saline following each AMPH injection, but only the Ara‐C group displayed behavioral sensitization across repeated AMPH exposure. At the high dose of AMPH (4 mg/kg), only mice treated with Ara‐C spent significantly more time on the AMPH‐paired side. All groups showed a higher activity level following the first AMPH injection compared to baseline. Findings suggest that sensitivity to the rewarding and locomotor effects of AMPH is enhanced following early treatment with MTX and Ara‐C. Since these effects were observed at a lower AMPH dose compared to the saline‐treated group, it may be that the dose‐response curve for AMPH has shifted following early chemotherapeutic treatment. (Supported by CA129092 and T32 DA07237).