Behavioural and hypothalamic molecular effects of the anti-cancer agent cisplatin in the rat: A model of chemotherapy-related malaise?

Many cancer patients receiving chemotherapy experience fatigue, disturbed circadian rhythms, anorexia and a variety of dyspeptic symptoms including nausea. There is no animal model for this ‘chemotherapy-related malaise’ so we investigated the behavioural and molecular effects of a potent chemothera...

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Veröffentlicht in:Pharmacology, biochemistry and behavior biochemistry and behavior, 2006, Vol.83 (1), p.9-20
Hauptverfasser: Malik, N.M., Moore, G.B.T., Smith, G., Liu, Y.-L., Sanger, G.J., Andrews, P.L.R.
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Sprache:eng
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Zusammenfassung:Many cancer patients receiving chemotherapy experience fatigue, disturbed circadian rhythms, anorexia and a variety of dyspeptic symptoms including nausea. There is no animal model for this ‘chemotherapy-related malaise’ so we investigated the behavioural and molecular effects of a potent chemotherapeutic agent, cisplatin (CP, 6 mg/kg, i.p.) in rats. Dark-phase horizontal locomotor activity declined post-CP reaching a nadir on day 3 ( P < 0.001), before recovering after 7 days. CP's effect was most marked in the late part (05.00–07.00) of the dark-phase. Food intake reached a nadir ( P > 0.001) at 2 days, coincident with an increase in gastric contents (cisplatin 9.04 ± 0.8 vs. saline 2.32 ± 0.3 g; P < 0.001). No changes occurred in hypothalamic mRNA expression for AGRP, NPY, HCRT, CRH, IL-1, IL-6, TNFα, ABCG1, SLC6A4, PPIA and HPRT mRNA but tryptophan hydroxylase (TPH) mRNA was decreased (47%, P < 0.05) at day 21 post-CP. This shows that despite marked behavioural effects of cisplatin, only a discrete change (TPH) was found in hypothalamic mRNA expression and that occurred when the animals' behaviour had recovered. Findings are discussed in relation to the neuropharmacology of chemotherapy-induced malaise.
ISSN:0091-3057
1873-5177
DOI:10.1016/j.pbb.2005.11.017