Effect of nitric oxide synthase inhibitor L-NAME on fear extinction in rats

Abstract

Objective To investigate the effects of nitric oxide synthase inhibitor L-NAME on two tone fear extinction design in rats. Methods In AAA design, the rats received fear conditioning, extinction training and extinction test in the same context. In AAB design, the rats received fear conditioning and extinction training in context A, extinction test in context B. In each task, 40 male rats were randomly divided into 4 groups(n=10 per group), and L-NAME(10, 20 and 40 mg/kg) or saline was injected intraperitoneally (i.p) 30 min prior to extinction training.Percent freezing was used as an index for fear memory during extinction test phases.Further experiments were used to test state-dependency effects or nonspecific changes of locomotor activity that followed L-NAME injection. Results In AAA design, percent freezing was (27.42±6.52)% in saline group, and (30.83±7.15)%, (32.49±8.55)%, (38.94±11.48)% in 10, 20, 40 mg/kg L-NAME group respectively. There was no significant difference in the level of percent freezing among the four groups (P>0.05). In AAB design, percent freezing was (30.32±6.15)% in saline group, and (32.83±6.64)%, (39.49±8.74)%, (49.94±10.83)% in 10, 20, 40 mg/kg L-NAME group respectively.Compared with saline, only rats with L-NAME 40 mg/kg showed more levels of freezing (P<0.01). In state-dependency effects test, compared with Sal-Sal group((26.73±5.62)%) which received both saline injections 30 min before extinction training and extinction test, respectively, both NAME-Sal group((48.44±10.46)%) and NAME-NAME group((61.25±13.24)%) showed more levels of freezing (P<0.01, respectively). Conclusion These results show that L-NAME produces a task-dependent impairment of fear extinction, and imply that nitric oxide signaling is involved in memory process of certain extinction tasks. Key words: Nitric oxide; Fear extinction; Freezing; Learning; Memory