Lipopolysaccharide-Induced Sickness Behaviour Evaluated in Different Models of Anxiety and Innate Fear in Rats

Author(s)

Bassi, Gabriel S. ^{[1, 2]} ; Kanashiro, Alexandre ^[3] ; Santin, Francele M. ^{[1, 2]} ; de Souza, Gloria E. P. ^[3] ; Nobre, Manoel J. ^{[1, 2]} ; Coimbra, Norberto C. ^{[1, 4]}

Affiliation

^[1] Univ Sao Paulo, Inst Neurosci & Behav INeC, Sao Paulo - Brazil

^[2] Univ Sao Paulo FFCLRP USP, Lab Psychobiol, Sch Philosophy Sci & Literature Ribeirao Preto, Sao Paulo - Brazil

^[3] Univ Sao Paulo FCFRP USP, Sch Pharmaceut Sci Ribeirao Preto, Dept Phys & Chem, Sao Paulo - Brazil

^[4] Univ Sao Paulo FMRP USP, Lab Neuroanat & Neuropsychobiol, Dept Pharmacol, Sch Med Ribeirao Preto, BR-14049900 Ribeirao Preto, SP - Brazil

• Document type: Journal article
• Source: BASIC & CLINICAL PHARMACOLOGY & TOXICOLOGY; v. 110, n. 4, p. 359-369, APR 2012.
• Web of Science Citations: 46

Abstract

The fact that there is a complex and bidirectional communication between the immune and nervous systems has been well demonstrated. Lipopolysaccharide (LPS), a component of gram-negative bacteria, is widely used to systematically stimulate the immune system and generate profound physiological and behavioural changes, also known as sickness behaviour (e.g. anhedonia, lethargy, loss of appetite, anxiety, sleepiness). Different ethological tools have been used to analyse the behavioural modifications induced by LPS; however, many researchers analysed only individual tests, a single LPS dose or a unique ethological parameter, thus leading to disagreements regarding the data. In the present study, we investigated the effects of different doses of LPS (10, 50, 200 and 500 mu g/kg, i.p.) in young male Wistar rats (weighing 180200 g; 89 weeks old) on the ethological and spatiotemporal parameters of the elevated plus maze, light-dark box, elevated T maze, open-field tests and emission of ultrasound vocalizations. There was a dose-dependent increase in anxiety-like behaviours caused by LPS, forming an inverted U curve peaked at LPS 200 mu g/kg dose. However, these anxiety-like behaviours were detected only by complementary ethological analysis (stretching, grooming, immobility responses and alarm calls), and these reactions seem to be a very sensitive tool in assessing the first signs of sickness behaviour. In summary, the present work clearly showed that there are resting and alertness reactions induced by opposite neuroimmune mechanisms (neuroimmune bias) that could lead to anxiety behaviours, suggesting that misunderstanding data could occur when only few ethological variables or single doses of LPS are analysed. Finally, it is hypothesized that this bias is an evolutionary tool that increases animals security while the body recovers from a systemic infection. (AU)

• FAPESP's process: 09/00668-6 - Study of the involvement of cholinergic pathways form tegmentar pedunculopontine nucleus to monoaminergic nuclei of the pain endogenous inhibitory system in the post-ictal antinociception
• Grantee: Norberto Cysne Coimbra
• Support Opportunities: Regular Research Grants