Evaluation of functional relationship between mouse hippocampal cholinergic and nitrergic systems in anxiogenic-like behavior

Abstract

Although a body of evidence shows the crucial role of hippocampal nitrergic and cholinergic systems in the modulation of anxiety, little is known about their functional relationship with regard to anxiety. The present study investigated the relationship between intra-CA1 administration of a nicotinic acetylcholine receptor antagonist (mecamylamine) and a nitric oxide synthase inhibitor [Nω-nitro-L-arginine methyl ester (L-NAME)] or its precursor (L-arginine) in anxiety-related behaviors. Mice received bilateral intra-CA1 injections of either L-NAME or L-arginine in the presence of mecamylamine and were subsequently tested in the elevated plus maze. A dose of 0.5 μg/0.5 μl mecamylamine bilaterally administered into CA1 did not change the percentage of open arm time (%OAT) or the percentage of open arm entries (%OAE) in the elevated plus maze task and thus was considered as a subeffective dose. Intra-CA1 administration of either L-arginine (1 and 1.5 μg/0.5 μl, bilaterally) or L-NAME (at 60 ng/0.5 μl, bilaterally) decreased %OAT, which represents an anxiogenic-like effect. Coadministration of the subeffective dose of mecamylamine together with the lower doses of L-NAME (10 and 30 ng/0.5 μl, bilaterally) or L-arginine (0.5 μg/0.5 μl, bilaterally) led to a decrease in %OAT and %OAE. Thus, both L-NAME and L-arginine showed anxiogenic-like effects, but the effects of mecamylamine were too small to support a functional relationship between the hippocampal cholinergic and nitrergic systems.

Anxiety- and depression-like phenotype of hph-1 mice deficient in tetrahydrobiopterin

“…Indeed, hph mice in this study displayed ∼75% lower plasma nitrite and nitrate concentrations, an index of NO production, compared to WT mice, which is in line with other studies showing markedly reduced NO levels in hph-1 mice (Barker et al, 1998;Lam et al, 2007). In the elevated plus maze test (EPM, the precurser to the EZM), neuronal NO synthase knock-out mice displayed increased anxiety-like behaviours (Weitzdoerfer et al, 2004), and studies in both rats and mice have reported anxiogenic-like effects of NOS inhibitors in the EPM Vale et al, 1998;Zarrindast et al, 2013). While this could indicate that the increased anxiety-like behaviour observed in hph mice is linked to low NO levels, other studies have shown anxiolytic-like properties of NOS inhibitors (Guimarães et al, 1994;Volke et al, 1995;Faria et al, 1997;Spiacci et al, 2008).…”