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Anxiolytic effects induced by inhibition of the nitric oxide–cGMP pathway in the rat dorsal hippocampus

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Abstract

Rationale

Conflicting results have been reported regarding the role of the nitric oxide (NO)–cyclic guanosine monophosphate (cGMP) pathway in the hippocampus on anxiety modulation.

Objectives

To investigate the effects of intrahippocampal injections of drugs that modify the NO–cGMP pathway in rats submitted to two animal models that are sensitive to anxiolytic drugs, the elevated plus-maze and the Vogel punished licking test.

Materials and methods

Male Wistar rats with cannulae aimed at the dentate gyrus of the dorsal hippocampus received microinjections of the NO synthase (NOS) inhibitors N G-nitro-L-arginine methyl ester (LNAME, 15–300 nmol/0.2 μl), N G-nitro-L-arginine (LNOARG, 50–300 nmol/0.2 μl), 7-nitroindazole (7NI, 10–100 nmol/0.2 μl), or the soluble guanylate cyclase inhibitor 1H-oxadiazolo-quinoxalin-1 one (ODQ, 10–100 nmol/0.2 μl), and were submitted to the elevated plus-maze. In a second group, the animals received 7NI, LNAME, or ODQ and were submitted to the Vogel punished licking test. To control for drug-induced changes in locomotor behavior, the animals were submitted to an open arena or to the Rota-rod test.

Results

All drugs increased the exploration of the open arms of the elevated plus-maze. They also increased the number of punished licks in the Vogel test, indicating an anxiolytic effect. The anxiolytic effect of LNAME was prevented by previous treatment with L-arginine (300 nmol/0.2 μl). Except for the lower dose of LNAME (15 nmol), administration of the NOS inhibitors or ODQ did not change exploratory activity in the open field nor cause any gross locomotor impairment in the Rota-rod test.

Conclusion

The results suggest that NO plays an anxiogenic role in the dentate gyrus of the dorsal hippocampus.

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Abbreviations

NMDA:

N-methyl-D-aspartate

NADPH:

nicotinamide adenine dinucleotide phosphate

NOS:

nitric oxide synthase

sGC:

soluble guanylate cyclase enzyme

dlPAG:

dorsolateral periaqueductal gray matter

7NI:

7-nitroindazole

cGMP:

cyclic guanosine monophosphate

LNOARG:

NG-nitro-l-arginine

LNAME:

NG-nitro-L-arginine methyl ester hydrochloride

ODQ:

1H-oxadiazolo-quinoxalin-1 one

DMSO:

dimethyl sulfoxide

ANOVA:

one-way analysis of variance

CA:

Ammon’s horn

5-HT:

5-hidroxy-tryptamine

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Acknowledgements

The authors acknowledge the helpful technical support provided by C.A. Silva and R. Ferreira. The study was supported by grants from Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) and the Fundação de Amparo à Pesquisa do Estado de São Paulo (Fapesp).

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Authors and Affiliations

  1. Department MEF-Physiology, School of Odontology, Campus USP Ribeirão Preto, 14049-904, Ribeirão Preto, SP, Brazil

    P. C. M. Spolidório, M. B. Echeverry, M. Iyomasa & E. A. Del Bel

  2. Department of Pharmacology, Medical School, Campus USP Ribeirão Preto, Ribeirão Preto, SP, Brazil

    F. S. Guimarães

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  1. P. C. M. Spolidório
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  2. M. B. Echeverry
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Correspondence to M. B. Echeverry.

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Spolidório, P.C.M., Echeverry, M.B., Iyomasa, M. et al. Anxiolytic effects induced by inhibition of the nitric oxide–cGMP pathway in the rat dorsal hippocampus. Psychopharmacology 195, 183–192 (2007). https://doi.org/10.1007/s00213-007-0890-0

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