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Rheumatology 2000; 39: 764-771
© 2000 British Society for Rheumatology

Onset and severity of inflammation in rats exposed to the learned helplessness paradigm

A. J. Chover-Gonzalez, D. S. Jessop1, P. Tejedor-Real, J. Gibert-Rahola and M. S. Harbuz1,

Department of Neuroscience, University of Cadiz, Spain,
1 Division of Medicine, University of Bristol, BRI, Marlborough Street, Bristol BS2 8HW, UK

Objective. To test the hypothesis that there is an association between susceptibility to inflammation and a hyporesponsive hypothalamo-pituitary-adrenal (HPA) axis.

Methods. Animals were separated on the basis of behaviour in the learned helplessness (LH) paradigm into groups of LH(+) (i.e. animals which did not escape footshock) and LH(-) animals. Adjuvant-induced arthritis (AA) was subsequently induced in the LH(+) and LH(-) animals.

Results. Plasma corticosterone was significantly increased in response to the LH test in the LH(-) compared with the LH(+) rats. We observed an earlier onset and increased inflammation in the LH(-) rats in spite of the greater corticosterone response to the acute stress. We noted lower levels of plasma testosterone in the LH(-) animals suggesting a possible influence for this protective factor in AA.

Conclusion. These data suggest that increased onset and severity of inflammation in AA is not a simple consequence of an attenuated HPA axis response to stress as proposed in the Lewis rat. Indeed we have observed the converse. Together these data suggest that the balance of pro- and anti-inflammatory factors released in response to stress may influence the progress of AA.

KEY WORDS: Learned helplessness, Adjuvant-induced arthritis, Inflammation, HPA axis, Corticosterone, Testosterone, Behaviour.

Correspondence to: M. S. Harbuz, Division of Medicine, University of Bristol, BRI, Marlborough Street, Bristol BS2 8HW, UK.


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