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


OBJECTIVE
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.


METHODS
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.


RESULTS
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.


CONCLUSIONS
The present results suggest that inhibition of NO formation in the MeA produces anxiolytic-like effect in rats.
Forestiero
Daniel
D
Department of Pharmacology, University of Maringá, Av. Colombo 5790, 87020-900, Maringá, Parana, Brazil.
Manfrim
Carlos Mora
CM
Guimarães
Francisco Silveira
FS
de Oliveira
Rúbia Maria Weffort
RM
D000679:Amygdala / Q000502:physiology*; D000818:Animals; D014151:Anti-Anxiety Agents; D001007:Anxiety / Q000523:psychology; D001120:Arginine / Q000494:pharmacology; D003624:Darkness; D004791:Enzyme Inhibitors / Q000008:administration & dosage / Q000494:pharmacology*; D007191:Indazoles / Q000494:pharmacology; D008027:Light; D008297:Male; D008845:Microinjections; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D052248:Nitric Oxide Synthase Type I / Q000037:antagonists & inhibitors*; D010487:Periaqueductal Gray; D051381:Rats; D017208:Rats, Wistar
D014151:Anti-Anxiety Agents; D004791:Enzyme Inhibitors; D007191:Indazoles; D001120:Arginine; D052248:Nitric Oxide Synthase Type I; C080122:7-nitroindazole; D019331:NG-Nitroarginine Methyl Ester