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 (2mg/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. (C) 2007 Elsevier B.V. All rights reserved.