Stress and anxious-related behaviors in Lurcher mutant mice.

Blood corticosterone levels (CORT) were measured before and after the completion of the elevated +-maze test in cerebellar Lurcher mutant and control mice. Consistent with the existence of a much more pronounced activation of the hypothalamo-pituitary-adrenal (HPA) system in the mutants, our results showed that while basal CORT were similar in mutants and controls, the surge of this stress indicator was enhanced in the Lurcher mice after completion of a behavioral test of anxiety. In contrast, at the behavioral level, we also observed that Lurcher exhibited significantly reduced anxiety related indices; they spent a significant greater amount of time in the aversive places of the apparatus and entered them more frequently than non mutant mice. It is proposed that rather than less anxious, the Lurcher mice are less inhibited than controls when placed in anxiogenic situation and that such poor inhibition could be causally related to changes in HPA system regulation. The overall patterns of our behavioral and endocrinological results thereby provided the evidence that cerebellar circuitry is involved in producing changes in physiological and behavioral stress-related emotional responses.