Altered emotionality, spatial memory and cholinergic function in caveolin-1 knock-out mice

Neurological phenotypes associated with loss of caveolin 1 (cav-1) (the defining structural protein in caveolar vesicles, which regulate signal transduction and cholesterol trafficking in cells) in mice have been reported recently. In brain, cav-1 is highly expressed in neurons and glia. We investigated emotional and cognitive behavioural domains in mice deficient in cav-1 (CavKO mice). CavKO mice were more anxious and spent more time in self-directed grooming behaviour than wild-type (wt) mice. In a spatial/working memory task, CavKO mice failed to recognize the object displacement, thus showing a spatial memory impairment. CavKO mice showed higher locomotor activity than wt mice, thus suggesting reduced inhibitory function by CNS cholinergic systems. Behavioural response to the cholinergic muscarinic antagonist, scopolamine (2 mg/Kg), was decreased in CavKO mice. Few behavioural sex differences emerged in mice; whereas the sex differences were generally attenuated or even reverted in the null genotype. Our data confirm a distinct behavioural phenotype in CavKO mice and indicate a selective alteration in central cholinergic function.