| First Author | Latapy C | Year | 2012 |
| Journal | Philos Trans R Soc Lond B Biol Sci | Volume | 367 |
| Issue | 1601 | Pages | 2460-74 |
| PubMed ID | 22826345 | Mgi Jnum | J:287783 |
| Mgi Id | MGI:6423647 | Doi | 10.1098/rstb.2012.0094 |
| Citation | Latapy C, et al. (2012) Selective deletion of forebrain glycogen synthase kinase 3beta reveals a central role in serotonin-sensitive anxiety and social behaviour. Philos Trans R Soc Lond B Biol Sci 367(1601):2460-74 |
| abstractText | 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 3beta (GSK3beta). Furthermore, GSK3beta 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 GSK3beta activity in the regulation of behaviour, we generated CamKIIcre-floxGSK3beta mice in which the gsk3b gene is postnatally inactivated in forebrain pyramidal neurons. Behavioural characterization showed that suppression of GSK3beta in these brain areas has anxiolytic and pro-social effects. However, while a global reduction of GSK2beta expression reduced responsiveness to amphetamine and increased resilience to social defeat, these behavioural effects were not found in CamKIIcre-floxGSK3beta mice. These findings demonstrate a dissociation of behavioural effects related to GSK3 inhibition, with forebrain GSK3beta 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. |
