ABSTRACT
Objective To explore the effect of citalopram on tau phosphorylation and memory defi-cits induced by social isolation (SI) in adult rats.Methods Sixty Sprague-Dawley adult rats (8 months) were grouped or isolation reared for six-weeks.Following the initial two-week period of rearing, citalopram ( 10 mg/kg,i.p.) was administered for 4 weeks.Novel object recognition test,Western blot and ELISA were used to detect recognitive function,the levels of tau and GSK-3βprotein,and melatonin level respectively. Results In the novel object recognition test,compared with the citalopram group(0.71±0.05) and housed group(0.73±0.13),discrimination ratio(0.48±0.15) in SI group was significant decreased (P<0.05).Tau hyperphosphorylation at Tau-1 ((0.88±0.11)),Ser396 (3.94±0.74) episodes were found and almost re-versed by citalopram at Tau-1 (1.56±0.17),Ser396 (2.31±0.24) episodes in SI group.Compared with GH group,the total level of GSK-3β(1.12±0.09) was significantly increased,while the level of Ser9-phosphoryl-ated GSK-3β(inactive form) (0.47±0.11) was significantly decreased in the SI group,both of which were reversed by citalopram (GSK-3β(0.87±0.08) and Ser9-phosphorylated GSK-3β(0.80±0.07)).The me-latonin level was decreased in SI group ((359.54±18.80)pg/ml),and citalopram could partly restore the level of melatonin (418.15±18.72)pg/ml, P<0.05).Conclusion The results demonstrate that citalopram increases the level of melatonin which negatively regulates GSK-3βand attenuates tau hyperphosphorylation and memory deficits induced by SI in adult rats.