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

Abstract

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, TNFalpha, 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.

• Authors: N M Malik, G B T Moore, G Smith, Y-L Liu, G J Sanger, P L R Andrews
• Journal: Pharmacology, biochemistry, and behavior (Pharmacol Biochem Behav) Vol. 83 Issue 1 Pg. 9-20 (Jan 2006) ISSN: 0091-3057 [Print] United States
• PMID: 16443263 (Publication Type: Journal Article)

Chemical References

• Antineoplastic Agents
• RNA, Messenger
• Cisplatin

Topics

• Animals
• Antineoplastic Agents (adverse effects, pharmacology)
• Behavior, Animal (drug effects)
• Body Weight (drug effects)
• Cisplatin (adverse effects, pharmacology)
• Disease Models, Animal
• Drinking (drug effects)
• Eating (drug effects)
• Gastrointestinal Contents (drug effects)
• Hypothalamus (drug effects, metabolism)
• Male
• Motor Activity (drug effects)
• RNA, Messenger (biosynthesis, genetics)
• Rats
• Rats, Wistar
• Reverse Transcriptase Polymerase Chain Reaction