title: Early age-related cognitive impairment in mice lacking cannabinoid CB1 receptors.
abstract: The molecular mechanisms contributing to the normal age-related decline of cognitive functions or to pathological learning and memory impairment are largely unknown. We demonstrate here that young mice (6-7 weeks) with a genetic deletion of the cannabinoid CB1 receptor performed as well as WT mice, or often better, in a number of learning and memory paradigms, including animal models of skill-learning, partner recognition, and operant conditioning. In contrast, the performance of mature mice (3-5 months) lacking CB1 receptors was much worse than that of age-matched WT animals. In most tests, these mice performed at the same level as old animals (14-17 months), suggesting that the decline in cognitive functions is accelerated in the absence of CB1 receptors. This rapid decline in CB1-deficient animals is accompanied by a loss of neurons in the CA1 and CA3 regions of the hippocampus.
authors.affiliation: Laboratory of Molecular Neurobiology, Department of Psychiatry, University of Bonn, Sigmund-Freud-Strasse 25, 53105 Bonn, Germany.
authors.forename: A
authors.initials: A
authors.lastname: Bilkei-Gorzo
authors.forename: I
authors.initials: I
authors.lastname: Racz
authors.forename: O
authors.initials: O
authors.lastname: Valverde
authors.forename: M
authors.initials: M
authors.lastname: Otto
authors.forename: K
authors.initials: K
authors.lastname: Michel
authors.forename: M
authors.initials: M
authors.lastname: Sastre
authors.forename: M
authors.initials: M
authors.lastname: Sarstre
authors.forename: A
authors.initials: A
authors.lastname: Zimmer
mesh_terms: D000375:Aging / Q000523:psychology*; D000818:Animals; D002452:Cell Count; D003072:Cognition Disorders / Q000209:etiology*; D003216:Conditioning, Operant; D006624:Hippocampus / Q000473:pathology; D007858:Learning; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009043:Motor Activity; D009474:Neurons / Q000473:pathology; D046709:Pattern Recognition, Physiological; D043884:Receptor, Cannabinoid, CB1 / Q000235:genetics / Q000502:physiology*
chemical_list: D043884:Receptor, Cannabinoid, CB1