title: Behavioural phenotyping reveals anxiety-like features of SV2A deficient mice.
abstract: Synaptic vesicle protein 2A (SV2A) is involved in neurotransmitter release and has been identified as the binding site for levetiracetam (Keppra), a novel antiepileptic drug. Homozygous SV2A (-/-) mice are not viable beyond a few weeks. In contrast, heterozygous SV2A (+/-) mice have a normal lifespan. We performed a behavioural phenotyping on SV2A (+/-) mice in a battery of tests: gross behavioural observation, spontaneous locomotor activity, sensori-motor coordination, acute pain sensitivity, exploration in an elevated plus-maze and an assessment of learning abilities in an inhibitory avoidance procedure. SV2A (+/-) mice were compared to age-matched, 2-month-old wild type controls. Overall, gross behaviour, spontaneous locomotor activity, sensori-motor coordination and acute pain sensitivity were comparable between wild type and SV2A (+/-) mice. When tested in a plus-maze, SV2A (+/-) mice displayed significant increased avoidance of open elevated arms whereas locomotor activity was not altered. Finally, both SV2A (+/-) and wild type mice showed comparable memory performance at the end of a multi-trial passive avoidance procedure. Interestingly, SV2A (+/-) mice exhibited increased avoidance of the lit area during the first sessions without foot shock. These results suggest an anxiety-like phenotype for SV2A (+/-) mice indicated by increased open-arm avoidance in the elevated plus-maze test as well as a shorter latency to escape from a lit area in the inhibitory avoidance procedure.
authors.affiliation: Preclinical CNS Research, UCB Pharma s.a., Braine-l'Alleud, Belgium. yves.lamberty@ucb-group.com
authors.forename: Yves
authors.initials: Y
authors.lastname: Lamberty
authors.forename: Eric
authors.initials: E
authors.lastname: Detrait
authors.forename: Karine
authors.initials: K
authors.lastname: Leclercq
authors.forename: Anne
authors.initials: A
authors.lastname: Michel
authors.forename: Marc
authors.initials: M
authors.lastname: De Ryck
mesh_terms: D000818:Animals; D001007:Anxiety / Q000503:physiopathology / Q000523:psychology*; D001362:Avoidance Learning; D001522:Behavior, Animal; D004558:Electric Stimulation / Q000009:adverse effects; D004924:Escape Reaction; D005106:Exploratory Behavior; D005838:Genotype; D018782:Maze Learning; D008562:Membrane Glycoproteins / Q000172:deficiency* / Q000235:genetics; D008568:Memory; D051379:Mice; D018345:Mice, Knockout; D009043:Motor Activity; D009419:Nerve Tissue Proteins / Q000172:deficiency* / Q000235:genetics; D010146:Pain / Q000503:physiopathology / Q000523:psychology; D017288:Pain Threshold / Q000523:psychology; D010641:Phenotype; D016133:Polymerase Chain Reaction
chemical_list: D008562:Membrane Glycoproteins; D009419:Nerve Tissue Proteins; C489614:Sv2a protein, mouse