Anxiolytic-like effects induced by nitric oxide synthase inhibitors microinjected into the medial amygdala of rats

Abstract

The amygdaloid complex plays a central role in the neuroanatomical circuits that coordinate defensive responses. Nitric oxide (NO) has been involved in the neurochemical, hormonal, and behavioral changes related to stress and anxiety. A high density of NO-producing neurons is observed in the medial amygdala (MeA). These neurons are activated after exposure to threatening stimuli such as a live predator. To test the hypothesis that microinjection into the MeA of two NO synthase inhibitors, NG-nitro-L-arginine methyl ester (L-NAME) or 7-nitroindazole (7-NI), would produce anxiolytic effects. Male Wistar rats (n=8-10/group) were submitted to stereotaxic surgery to implant bilateral stainless steel guide cannulae aimed at the MeA. Six days after the surgery, the animals received intra-MeA microinjections of the drugs or vehicle and, 10 min later, were submitted to the elevated plus-maze (EPM) or the light-dark transition procedures. Both L-NAME (50-200 nmol) and 7-NI (5 and 10 nmol) increased open-arm exploration in the EPM without changing the number of enclosed arm entries, indicating an anxiolytic-like effect. The anxiolytic-like effect of L-NAME (200 nmol) was prevented by pretreatment with L-arginine (100 nmol). Injections of 7-NI or L-NAME outside the MeA did not produce any significant change in EPM exploration. When tested in the light-dark test, L-NAME (200 nmol) or 7-NI (10 nmol) increased the time when the animal remained in the light compartment of the light-dark box. The present results suggest that inhibition of NO formation in the MeA produces anxiolytic-like effect in rats.