The long-term impact of oxaliplatin chemotherapy on rodent cognition and peripheral neuropathy

Joanna E Fardell; Janette Vardy; Lauren A Monds; Ian N Johnston

doi:10.1016/j.bbr.2015.04.038

The long-term impact of oxaliplatin chemotherapy on rodent cognition and peripheral neuropathy

Behav Brain Res. 2015 Sep 15:291:80-88. doi: 10.1016/j.bbr.2015.04.038. Epub 2015 Apr 28.

Authors

Joanna E Fardell¹, Janette Vardy², Lauren A Monds³, Ian N Johnston⁴

Affiliations

¹ School of Psychology, The University of Sydney, Australia. Electronic address: joanna.fardell@sydney.edu.au.
² Concord Cancer Centre, Concord General Repatriation Hospital, Sydney Medical School, The University of Sydney. Electronic address: janette.vardy@sydney.edu.au.
³ Discipline of Addiction Medicine, Central Clinical School, Sydney Medical School, The University of Sydney. Electronic address: lauren.monds@sydney.edu.au.
⁴ School of Psychology, The University of Sydney, Australia. Electronic address: i.johnston@sydney.edu.au.

PMID: 25934489
DOI: 10.1016/j.bbr.2015.04.038

Abstract

Chemotherapy treatment is associated with cognitive dysfunction in cancer survivors after treatment completion. The duration of these impairments is unclear. Therefore this paper aims to evaluate the lasting impact of varying doses of the chemotherapy oxaliplatin (OX) on cognition and peripheral neuropathy. In Experiment 1 rats were treated once a week for 3 weeks with either physiological saline (control) or 6 mg/kg OX i.p. and were assessed for peripheral neuropathy, using von Frey filaments, and cognitive function, using novel object and location recognition, up to 2 weeks after treatment completion. For Experiment 2 rats received 3 weekly i.p. injections of either physiological saline (control), 0.6 mg/kg, 2mg/kg or 6 mg/kg OX and assessed for peripheral neuropathy and cognitive function up to 11 months after treatment completion. Systemic OX treatment induced lasting effects on cognitive function at 11 months after treatment, and peripheral neuropathy at 1 month after treatment and these were dose dependent; higher doses of OX resulted in worse cognitive outcomes and more severe peripheral neuropathy.

Keywords: Chemotherapy; Cognition; Mechanical allodynia; Oxaliplatin; Peripheral neuropathy; Rat.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Antineoplastic Agents / toxicity*
Body Weight / drug effects
Cognition Disorders / chemically induced*
Disease Models, Animal
Dose-Response Relationship, Drug
Hyperalgesia / chemically induced
Hyperalgesia / physiopathology
Male
Organoplatinum Compounds / toxicity*
Oxaliplatin
Peripheral Nervous System Diseases / chemically induced*
Peripheral Nervous System Diseases / physiopathology
Rats, Wistar
Recognition, Psychology / drug effects
Time Factors
Touch

Substances

Antineoplastic Agents
Organoplatinum Compounds
Oxaliplatin