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Post-treatment with cotinine improved memory and decreased depressive-like behavior after chemotherapy in rats

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Cancer Chemotherapy and Pharmacology Aims and scope Submit manuscript

Abstract

Purpose

Most cancer patients treated with systemic adjuvant chemotherapy endure long-lasting side effects including decrease in concentration, forgetfulness and slower thinking, which are globally termed “chemobrain.” Cotinine, the main derivative of nicotine, improved visual and spatial working memory and decreased depressive-like behavior in an animal model of chemotherapy-induced cognitive impairment.

Methods

In this study, we investigated the effect of cotinine on weight gain, locomotor activity, cognitive abilities and depressive-like behavior in rats treated with the chemotherapy mix, cyclophosphamide, methotrexate and 5-fluorouracil. Locomotor activity and depressive-like behavior were assessed using the rotarod and Porsolt’s tests, respectively. Changes in cognitive abilities were determined using the novel place recognition test.

Results

Female rats treated with cotinine after chemotherapy, recovered weight faster, showed superior cognitive abilities and lower levels of depressive-like behavior than chemotherapy, vehicle-treated rats.

Conclusions

This evidence suggests that treatment with cotinine may facilitate the recovery and diminish the cognitive consequences of chemotherapy.

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Abbreviations

AD:

Alzheimer’s disease

ANOVA:

Analysis of variance

CMF:

Cyclophosphamide, methotrexate and 5-fluorouracyl

CYP:

Cytochrome P450

DG:

Dentate gyrus

DI:

Discrimination index

FANFT:

N-[4-(5-nitro-2-furyl)-2-thiazolyl] formamide

GSK3β:

Glycogen synthase kinase 3 beta

IP:

Intraperitoneal

IL:

Interleukin

MRI:

Magnetic resonance imaging

nAChR:

Nicotinic acetylcholine receptor

NLR:

Novel location recognition

PI3K:

Phosphoinositide-3 kinase

PT:

Porsolt’s test

Akt:

Protein kinase B

TNF:

Transforming neurotrophic factor

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Acknowledgments

This material is the result of work supported with resources and the use of facilities at the Bay Pines VA Healthcare System. The contents do not necessarily represent the views of the Department of Veterans Affairs or the United States Government. This work was in part supported by the Bay Pines Foundation and the grant Fondecyt 1150194 (to VE).

Author information

Authors and Affiliations

  1. Facultad de ciencias de la Salud, Universidad San Sebastián, Lientur 1457, 4080871, Concepción, Chile

    Alexandre Iarkov & Valentina Echeverria

  2. Department of Veterans Affairs, Bay Pines VA Healthcare System, Bay Pines, FL, 33744, USA

    Doreen Appunn

  3. Department of Veterans Affairs, Bay Pines VA Healthcare System, 10,000 Bay Pines Blvd. Bldg. 22, Rm. 123, Bay Pines, FL, 33744, USA

    Valentina Echeverria

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  1. Alexandre Iarkov
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Correspondence to Valentina Echeverria.

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Iarkov, A., Appunn, D. & Echeverria, V. Post-treatment with cotinine improved memory and decreased depressive-like behavior after chemotherapy in rats. Cancer Chemother Pharmacol 78, 1033–1039 (2016). https://doi.org/10.1007/s00280-016-3161-0

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  • DOI: https://doi.org/10.1007/s00280-016-3161-0

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