Increased intermale aggression and neuroendocrine response in mice deficient for the neural cell adhesion molecule (NCAM).

Mice deficient for the neural cell adhesion molecule (NCAM) show morphological and behavioural abnormalities in the adult form, including a reduced size of the olfactory bulb, reduced exploratory behaviour, and deficits in spatial learning. Here we report increased aggressive behaviour of both homozygous (NCAM -/-) and heterozygous (NCAM +/-) male mutant mice towards an unfamiliar male intruding into their home cage. While plasma testosterone concentrations did not differ between genotypes before or after behavioural testing, corticosterone levels were higher in mutant residents than in wild-type (NCAM +/+) residents 30 min after encountering the intruder. Levels of c-fos mRNA, analysed to monitor neuronal activation, were similar in primary output structures of the olfactory bulb in NCAM-deficient and NCAM +/+ mice, but were increased in brain areas of the limbic system in both NCAM -/- and NCAM +/- mutant mice after the behavioural test. These results indicate that abnormalities in social behaviour correlate with enhanced neuronal activity in limbic brain areas and result in increased social stress in NCAM-deficient mice.