Elsevier

Neuroscience

Volume 92, Issue 1, August 1999, Pages 327-341
Neuroscience

Behavioral, neuroendocrine and serotonergic consequences of single social defeat and repeated fluoxetine pretreatment in the Lewis rat strain

https://doi.org/10.1016/S0306-4522(98)00742-8Get rights and content

Abstract

We have analysed some behavioral, neuroendocrine and serotonergic consequences of a single (30-min) social defeat followed by 14–18 h of sensory contact with the aggressor, in Lewis rats, an inbred strain highly sensitive to chronic social stressors [Berton O. et al. (1998) Neuroscience 82, 147–159]. In addition, we have investigated how the aforementioned consequences are affected by pretreatment with the selective serotonin reuptake inhibitor, fluoxetine (7.5 mg/kg/day for 21 days). A single social defeat triggered hypophagia and body weight loss, and increased anxiety in the elevated plus-maze. It did not affect baseline plasma adrenocorticotropic hormone levels and renin activity, but decreased plasma corticosterone levels. On the other hand, the responses of the latter variables to subsequent acute forced swim stress were blunted (corticosterone) or amplified (adrenocorticotropic hormone, renin activity) by prior defeat. The density of hippocampal serotonin transporters, but not that of hippocampal serotonin-1A and cortical serotonin-2A receptors, was decreased by a single social defeat; in addition, neither tryptophan availability and serotonin synthesis/metabolism, nor serotonin-1A autoreceptor-mediated functions (inhibition of serotonin synthesis, hyperphagia) were affected. Fluoxetine pretreatment diminished social defeat-induced hypophagia, body weight loss and anxiety without affecting these variables in control animals. This pretreatment increased plasma corticosterone levels in resting and acutely stressed rats, but abolished social defeat-elicited corticosterone hyporesponsiveness to acute forced swim stress. Except for a decrease in midbrain serotonin transporter density, fluoxetine did not affect the other serotonergic indices analysed herein, i.e. serotonin-1A and serotonin-2A receptor densities, serotonin synthesis/metabolism.

A single social defeat in Lewis rats produces behavioral and endocrine alterations that may model some aspects of human anxiety disorders. In this paradigm, prior fluoxetine treatment is endowed with adaptive behavioral, and possibly neuroendocrine, effects without affecting the key elements of central serotonergic systems analysed herein.

Section snippets

Experimental procedures

This work consisted of two series of experiments, the first examining various behavioral, neuroendocrine and neurochemical effects of SSD (protocol A), and the second analysing the influence of repeated fluoxetine administration on the aforementioned effects of social defeat (protocol B).

Resident–intruder interactions

All the intruders were defeated by residents (none of them being killed). The mean latency for the first fight was 683±252 s, the mean number of bites received was 4.16±0.74 and the mean number of submissive postures was 2.83±0.54.

Effects of a single social defeat on behavioral reactivity

Body weight growth and food intake were found to vary between experimental groups (F2,39=19.35, P<0.001 and F2,29=17.59, P<0.001, respectively). As shown by post hoc tests, these two variables were reduced significantly in defeated animals compared with collectively

Discussion

The present study has defined some behavioral, neuroendocrine and 5-HT-related effects of SSD, and analysed the influence of repeated fluoxetine pretreatment on these effects of SSD. Because genetic factors and stress are etiological determinants of mood disorders;44., 73. we used Lewis rats, i.e. anxious rats11., 76. highly sensitive to repeated social defeat.10 This study is thus unique in that it analysed an integrative set of responses to an ethological stressor in genetically selected

Conclusions

This study first emphasizes the usefulness of SSD in the Lewis rat strain as a promising animal model for the study of the biological determinants of inadaptation to stressors. In particular, the observation that post-traumatic stress disorder is associated with anxiety,83 blunting of the HPA axis93 and is sensitive to fluoxetine administration83 underlines the potential relevance of this animal model. Second, the present data allow us to reject the hypothesis of a change in the binding

Acknowledgements

This work was supported by INSERM, INRA and Conseil Régional d'Aquitaine. We wish to thank Y. Mellerin for taking care of the animals.

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