title: Wfs1-deficient mice display impaired behavioural adaptation in stressful environment.
abstract: Wfs1-deficient mice were generated by disrupting the 8th exon of Wfs1 gene. Reproduction rates of homozygous Wfs1-deficient mice were slightly below the expected values, they displayed intolerance to glucose and overall lower body weight. The present behavioural study was performed in female Wfs1-deficient mice due to their milder metabolic disturbances. Non-fasting blood glucose levels did not differ between homozygous Wfs1-deficient mice and wild-type littermates. While there was no difference in baseline plasma corticosterone, exposure to stress induced a nearly three-fold elevation of corticosterone in Wfs1-deficient mice in relation to wild-type littermates. Wfs1-deficient mice did not display obvious shortcomings in sensory and motor functioning as exemplified by intact responses in conditioned learning paradigms and rota-rod test. Locomotor activity of Wfs1-deficient mice was significantly lower only in brightly lit environment. Short-term isolation had a significant anxiogenic-like effect on the behaviour of Wfs1-deficient mice in dark/light exploration test. Lower exploratory activity of Wfs1-deficient mice in the plus-maze was antagonised by pre-treatment with diazepam (1 mg/kg), a GABA(A) receptor agonist. Wfs1-deficient mice displayed increased anxiety-like behaviour in hyponeophagia test. The locomotor stimulatory effects of amphetamine (2.5-7.5 mg/kg) and apomorphine (3 mg/kg) were significantly attenuated and facilitated, respectively, in Wfs1-deficient mice. There were no differences between Wfs1-deficient mice and wild-types in forced swimming behaviour and conditioned fear responses. Subtle impairments in reversal learning were apparent in Wfs1-deficient mice in the Morris water maze. Altogether, the present study demonstrates impaired behavioural adaptation of Wfs1-deficient mice in stress-inducing situations. It is likely that Wfs1 protein plays a major role in the behavioural adaptation mechanisms to novel and stressful environments.
authors.affiliation: Department of Physiology, University of Tartu, 19 Ravila Street, 50411 Tartu, Estonia.
authors.forename: Hendrik
authors.initials: H
authors.lastname: Luuk
authors.forename: Mario
authors.initials: M
authors.lastname: Plaas
authors.forename: Sirli
authors.initials: S
authors.lastname: Raud
authors.forename: Jürgen
authors.initials: J
authors.lastname: Innos
authors.forename: Silva
authors.initials: S
authors.lastname: Sütt
authors.forename: Helena
authors.initials: H
authors.lastname: Lasner
authors.forename: Urho
authors.initials: U
authors.lastname: Abramov
authors.forename: Kaido
authors.initials: K
authors.lastname: Kurrikoff
authors.forename: Sulev
authors.initials: S
authors.lastname: Kõks
authors.forename: Eero
authors.initials: E
authors.lastname: Vasar
mesh_terms: D000223:Adaptation, Psychological; D000661:Amphetamine / Q000008:administration & dosage / Q000494:pharmacology; D000818:Animals; D001007:Anxiety / Q000523:psychology*; D001058:Apomorphine / Q000008:administration & dosage / Q000494:pharmacology; D000697:Central Nervous System Stimulants / Q000008:administration & dosage / Q000494:pharmacology; D003214:Conditioning, Classical; D003345:Corticosterone / Q000097:blood; D003975:Diazepam / Q000008:administration & dosage / Q000494:pharmacology; D018491:Dopamine Agonists / Q000008:administration & dosage / Q000494:pharmacology; D005106:Exploratory Behavior / Q000187:drug effects; D005239:Fear / Q000523:psychology; D005260:Female; D018757:GABA Modulators / Q000008:administration & dosage / Q000494:pharmacology; D005838:Genotype; D018782:Maze Learning / Q000187:drug effects; D008565:Membrane Proteins / Q000172:deficiency* / Q000235:genetics / Q000502:physiology*; D008568:Memory / Q000187:drug effects; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009043:Motor Activity / Q000187:drug effects; D016133:Polymerase Chain Reaction; D013312:Stress, Physiological
chemical_list: D000697:Central Nervous System Stimulants; D018491:Dopamine Agonists; D018757:GABA Modulators; D008565:Membrane Proteins; C114987:wolframin protein; D000661:Amphetamine; D001058:Apomorphine; D003975:Diazepam; D003345:Corticosterone