Male Fischer 344 and Lewis rats display differences in locomotor reactivity, but not in anxiety-related behaviours: relationship with the hippocampal serotonergic system.

Recent studies have shown that arthritis-susceptible Lewis female rats display a marked hypoactivity of the hypothalamo-pituitary-adrenal (HPA) axis and decreased concentrations of hippocampal serotonin receptors (5-HT1A), when compared with arthritis-resistant Fischer 344 female rats. Although previous studies have suggested that these inter-strain differences may extend to several behaviours, the hypothesis that Fischer 344 and Lewis differ in their anxiety and locomotor scores when placed in novel environments has been only scarcely tested. The present study has thus analysed the behaviours of male Fischer 344 and Lewis rats placed successively in activity cages, in an open field (low and high aversive conditions), and in two animal models of anxiety (the elevated plus-maze, the black/white box). Moreover, because the present study was conducted with male rats, we have also checked whether the HPA axis- and 5-HT1A receptor-related differences previously described between female Fischer 344 and Lewis rats extended to males. Under basal conditions: (i) activity of the HPA axis; and (ii) hippocampal 5-HT1A receptor binding and activity of tryptophan hydroxylase (the rate-limiting enzyme in 5-HT biosynthesis) were decreased in Lewis rats, compared with Fischer 344 rats. In addition, the response of the HPA axis to a mild stress (10 min in a novel environment) was lower in Lewis rats than in Fischer 344. When placed in activity cages, Lewis rats displayed a lower locomotor activity, compared with Fischer 344 rats. In the open-field, Lewis rats cross a lower number of inner squares and groomed less than Fischer 344 rats. In the elevated plus-maze and in the black/white box, Fischer 344 and Lewis rats exhibited similar 'anxious' profiles as none of the rats visited the open arms (elevated plus-maze) and the white compartment (black/white box). This study, which extends earlier neurochemical and neuroendocrine findings in females, suggests that both strains display high levels of anxiety but markedly differ in their locomotor activities. Whether the latter strain difference is due to alterations in the HPA axis and/or the central serotonergic systems is an issue that remains to be explored.