Behaviour Research Of Nitric Oxide Signaling Mechanism On Fear Extinction

Objectives:The present study,adoptting classical fear conditioning and fear extinction model,was to explore the mechanism of nitric oxide signaling in fear extinction through systematically examining the effects of nitric oxide synthase inhibitor L-NAME on fear extinction in different patterns.Methods:The present experiments are composed of cued fear extinction and context extinction. Cued fear extinction contain AAA,ABA,ABB,ABC and AAB model according to the change of context where fear conditioning,extinction training and extinction test happen.The procedure in every model is composed of habitation,fear conditioning,extinction training and extinction test.For example ,the procedure in AAA model is as follows.On Day 1,rats were transported to context A to habituate them to the context; On Day 2(fear conditioning phase),Rats received six pairings of tone and foot shock in context A; The next day(extinction training phase),rats were injected with L-NAME(10 mg/kg,20 mg/kg and 40 mg/kg) or saline 30 min prior to sixteen tone-alone extinction trials in context A; On Day 4(recall test phase),rats received sixteen additional extinction trials in context A.In ABA model,fear conditioning occurs in context A,extinction occurs in context B,and extinction test occurs in context A.In ABB model,fear conditioning occurs in context A,extinction and extinction test occur in context B. In ABC model,fear conditioning occurs in context A,extinction occurs in context B,and extinction test occurs in context C. In AAB model,fear conditioning and extinction occur in context A, and extinction test occurs in context B.Context fear extinction comprise of foreground contextual design and background contextual design according to whether there are pairings of tone and foot shock. The procedure in every model also includs habitation,fear conditioning,extinction training and extinction test. For example,the procedure in foreground contextual design is as follows.On Day 1,rats were transported to context A to habituate them to the context; On Day 2(fear conditioning phase),rats received six footshocks without tone presentation in context A; On Day 3 (extinction training phase),rats were injected with L-NAME(10 mg/kg,20 mg/kg and 40 mg/kg) or saline 30 min prior to a 30 min extinction session in the same context; The next day (extinction test phase),rats received an additional 30 min extinction session.In background contextual design, the procedure is the same with that in foreground contextual design,except that rats received six pairings of tone and foot shock in fear conditioning phase.Freezing time induced by tone stimulus or context stimulus is used as index of behaviour test.Results:In AAA and ABA model, there was no significant difference in the level of percent freezing among the four groups on extinction test phase. In ABB,ABC and AAB model, compared with rats with saline, only rats with L-NAME 40 mg/kg showed more levels of freezing on extinction test phase. In foreground contextual design and Background contextual design,there was also no significant difference in the level of percent freezing among the four groups on extinction test phase.Conclusion:NOS inhibitor L-NAME selectively impaired fear extinction in ABB,ABC and AAB model,but not in AAA,ABA, foreground contextual and background contextual model.The results suggested L-NAME produced a task-dependent impairment of fear extinction, and implied that nitric oxide signaling was involved in memory process of certain extinction tasks.