Characterization of Maleimide-Based Glycogen Synthase Kinase-3 (GSK-3) Inhibitors as Stimulators of Steroidogenesis
MetadataShow full item record
Inhibition of GSK-3β has been well documented to account for the behavioral actions of the mood stabilizer lithium in various animal models of mood disorders. Recent studies have showed that genetic or pharmacological inhibition of GSK-3β resulted in anxiolytic-like and pro-social behavior. In our ongoing efforts to develop GSK-3β inhibitors for the treatment of mood disorders, SAR studies on maleimide-based compounds were undertaken. We present herein for the first time that some of these GSK-3β inhibitors, in particular analogues 1 and 9, were able to stimulate progesterone production in the MA-10 mouse tumor Leydig cell model of steroidogenesis without any significant toxicity. These two compounds were tested in the SmartCube behavioral assay and showed anxiolytic-like signatures following daily dose administration (50 mg/kg, ip) for 13 days. Taken together, these results support the hypothesis that GSK-3β inhibition could influence neuroactive steroid production thereby mediating the modulation of anxiety-like behavior in vivo.
Showing items related by title, author, creator and subject.
The reasoned action approach applied to health behavior: Role of past behavior and tests of some key moderators using meta-analytic structural equation modelingHagger, Martin; Polet, J.; Lintunen, T. (2018)Rationale: The reasoned action approach (RAA) is a social cognitive model that outlines the determinants of intentional behavior. Primary and meta-analytic studies support RAA predictions for multiple health behaviors. ...
Autonomous and controlled motivational regulations for multiple health-related behaviors: between- and within-participants analysesHagger, Martin; Hardcastle, S.; Chater, A.; Mallett, C.; Pal, Sebely; Chatzisarantis, N. (2014)Self-determination theory has been applied to the prediction of a number of health-related behaviors with self-determined or autonomous forms of motivation generally more effective in predicting health behavior than ...
An extension of the theory of planned behavior to predict immediate hedonic behaviors and distal benefit behaviorsCollins, A.; Mullan, Barbara (2011)The importance of understanding different behavior types is fundamental to changing patterns of dietary consumption toward optimal health. This study investigates fruit and vegetable (F&V) consumption as a distal benefit ...