, Volume 184, Issue 2, pp 166–172 | Cite as

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

  • Daniel Forestiero
  • Carlos Mora Manfrim
  • Francisco Silveira Guimarães
  • Rúbia Maria Weffort de Oliveira
Original Investigation



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.


Nitric oxide Medial amygdala Plus-maze Anxiety 7-NI l-NAME Light–dark box 


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Copyright information

© Springer-Verlag 2005

Authors and Affiliations

  • Daniel Forestiero
    • 1
  • Carlos Mora Manfrim
    • 1
  • Francisco Silveira Guimarães
    • 2
  • Rúbia Maria Weffort de Oliveira
    • 1
  1. 1.Department of PharmacologyUniversity of MaringáMaringáBrazil
  2. 2.Department of PharmacologyUniversity of São PauloRibeirao PretoBrazil

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