title: Selective deletion of forebrain glycogen synthase kinase 3β reveals a central role in serotonin-sensitive anxiety and social behaviour.
abstract: Serotonin (5-HT) neurotransmission is thought to underlie mental illnesses, such as bipolar disorder, depression, autism and schizophrenia. Independent studies have indicated that 5-HT or drugs acting on 5-HT neurotransmission regulate the serine/threonine kinase glycogen synthase kinase 3β (GSK3β). Furthermore, GSK3β inhibition rescues behavioural abnormalities in 5-HT-deficient mice with a loss-of-function mutation equivalent to the human variant (R441H) of tryptophan hydroxylase 2. In an effort to define neuroanatomical correlates of GSK3β activity in the regulation of behaviour, we generated CamKIIcre-floxGSK3β mice in which the gsk3b gene is postnatally inactivated in forebrain pyramidal neurons. Behavioural characterization showed that suppression of GSK3β in these brain areas has anxiolytic and pro-social effects. However, while a global reduction of GSK2β expression reduced responsiveness to amphetamine and increased resilience to social defeat, these behavioural effects were not found in CamKIIcre-floxGSK3β mice. These findings demonstrate a dissociation of behavioural effects related to GSK3 inhibition, with forebrain GSK3β being involved in the regulation of anxiety and sociability while social preference, resilience and responsiveness to psychostimulants would involve a function of this kinase in subcortical areas such as the hippocampus and striatum.
authors: Department of Psychiatry and Neuroscience,  Laval University, , Quebec City, Quebec,  Canada.
authors: Camille
authors: C
authors: Latapy
authors: Véronique
authors: V
authors: Rioux
authors: Matthieu J
authors: MJ
authors: Guitton
authors: Jean-Martin
authors: JM
authors: Beaulieu
mesh_terms: D000661:Amphetamine / Q000494:pharmacology; D000818:Animals; D014151:Anti-Anxiety Agents / Q000378:metabolism; D001007:Anxiety / Q000378:metabolism / Q000503:physiopathology*; D004789:Enzyme Activation; D005260:Female; D017353:Gene Deletion; D020868:Gene Silencing; D038362:Glycogen Synthase Kinase 3 / Q000235:genetics / Q000378:metabolism*; D000071679:Glycogen Synthase Kinase 3 beta; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D019964:Mood Disorders / Q000378:metabolism / Q000503:physiopathology; D009043:Motor Activity; D016548:Prosencephalon / Q000187:drug effects / Q000201:enzymology / Q000503:physiopathology*; D012701:Serotonin / Q000235:genetics / Q000378:metabolism*; D012919:Social Behavior; D013550:Swimming
chemical_list: D014151:Anti-Anxiety Agents; D012701:Serotonin; D000661:Amphetamine; C000605506:GSK3B protein, human; D000071679:Glycogen Synthase Kinase 3 beta; C000605507:Gsk3b protein, mouse; D038362:Glycogen Synthase Kinase 3