Endocrine Abstracts

Decreased anxiety-related behaviour and increased spatial memory retention in 11beta-hydroxysteroid dehydrogenase type 1 knockout mice

JL Yau¹, C Hibberd¹, J Paterson², JJ Mullins² & JR Seckl¹

¹Molecular Endocrinolgy Laboratory, Molecular Medicine Centre, University of Edinburgh, UK; ²Molecular Physiology Laboratory, Wilkie Building, University of Edinburgh, UK.

11beta-Hydroxysteroid dehydrogenase type 1 (11beta-HSD-1) is a key enzyme which amplifies intracellular levels of active glucocorticoids within specific tissues, including the brain. The hippocampus highly expresses both corticosteroid receptors and 11beta-HSD-1, making it a prime target for glucocorticoid actions. This brain region plays an important role in fear/anxiety behaviours and learning and memory. We examined the anxiety-related behaviours (elevated plus maze and open field) and spatial memory (Y-maze) in young (3 months) and middle-aged (12 months) male mice homozygous for targeted disruption of the 11beta-HSD-1 gene on the C57BL/6J background and wild type controls. Young 11beta-HSD-1 knockout mice displayed more open-protected stretches (43%, P < 0.05) in the elevated plus maze and showed greater locomotion (38%, p<0.01) in the 5 minute open field test than young wild type controls, suggesting subtly reduced anxiety related behaviour. Spatial memory retention [percentage time spent in the novel arm of the Y-maze after a 2 hour inter-trial interval (ITI)] was impaired (P<0.01) in middle-aged wildtype mice (31 plus/minus 3%) but maintained in middle-aged 11beta-HSD-1 knockout mice (46 plus/minus 4%). Basal plasma corticosterone levels were elevated in the 11beta-HSD-1 knockout mice compared to wildtype controls (P<0.01). These data suggest that circulating glucocorticoid levels are not the sole signal for glucocorticoid actions on brain function and that intracellular regeneration plays an important role.

Endocrine Abstracts (2003) 5 OC29