Complex interaction between anandamide and the nitrergic system in the dorsolateral periaqueductal gray to modulate anxiety-like behavior in rats

Author(s)

Lisboa, S. F. ; Magesto, A. C. ; Aguiar, J. C. ; Resstel, L. B. M. ; Guimaraes, F. S.

• Document type: Journal article
• Source: Neuropharmacology; v. 75, p. 9-pg., 2013-12-01.

Abstract

Stimulation of cannabinoid CBI receptors or inhibition of nitric oxide synthase (NOS) in the dorsolateral periaqueductal gray (dlPAG) decreases anxiety-like behavior. Moreover, activation of CBI receptors attenuates flight responses induced by nitric oxide (NO) donors in the dlPAG, suggesting that endocannabinoids and NO could interact to control defensive responses such as anxiety-like behavior. To test this hypothesis male Wistar rats received intra-dlPAG microinjections of anandamide (AEA) or NO inhibitors and were tested in the elevated plus maze (EPM). Combined administration of low and ineffective doses of AEA and the NO scavenger (c-Ptio), the nNOS inhibitor (NPA) or the soluble guanylate cyclase inhibitor (ODQ) induced anxiolytic-like effects. The CB1 receptor antagonist AM251, but not the GABA(A) receptor antagonist bicuculline, attenuated the effect induced by AEA + c-Ptio combination. No effect, however, was found when anxiolytic doses of these same drugs were administered together. Combination of higher, ineffective doses of AEA and c-Ptio, NPA or ODQ was again anxiolytic. The effect of the former combination was prevented by low and ineffective doses of the GABA(A) receptor antagonist bicuculline or the GABA synthesis inhibitor L-allilglycine, suggesting that they depend on GABA(A)-mediated neurotransmission. AM251 was also able to attenuate this effect, indicating that in the presence of NO inhibition, the resultant anxiolytic-like effect could be due to AEA action on CBI receptors. The present results suggest that the AEA and nitrergic systems exert a complex functional interaction in the dlPAG to modulate anxiety behavior, probably interfering, in addition to glutamate, also with GABAergic mechanisms. (C) 2013 Elsevier Ltd. All rights reserved. (AU)

• FAPESP's process: 07/06999-9 - Study of possible interaction between cannabinoid and nitrergic systems in the dorsolateral periaqueductal gray on modulation of defensive behaviors in rats
• Grantee: Sabrina Francesca de Souza Lisboa
• Support Opportunities: Scholarships in Brazil - Doctorate
• FAPESP's process: 11/08705-8 - Study of involvement of NMDA receptors/nitric oxide pathway in anxiolytic like-effect induced by dorsolateral periaquedutal gray matter endocanabinoid system observed in rats submitted to elevated plus maze
• Grantee: Amanda Conte Magesto
• Support Opportunities: Scholarships in Brazil - Scientific Initiation