Two alkaloids, erysodine (1) and erysothrine (2) were isolated from the flowers of a Pakistani medicinal plant, Erythrina suberosa. These compounds were investigated for anxiolytic properties, and the results showed significant effect, in an acute oral treatment with 1-2, which were suspended in saline (NaCl 0.9%) plus DMSO 1%, and evaluated in 122 Swiss male mice exposed to two tests of anxiety - the elevated plus-maze (EPM) and the light/dark transition model (LDTM).

Glutamate N-methyl-D-aspartate (NMDA) receptor activation within the dorsal column of the periaqueductal gray (dPAG) leads to antinociceptive, autonomic, and behavioral responses characterized as the fear reaction. Activation of NMDA receptors in the brain increases nitric oxide (NO) synthesis, and NO has been proposed to be a mediator of the aversive action of glutamate. This paper reviews a series of studies investigating the effects of neuronal NO synthase (nNOS) inhibition in the dPAG of mice in different aversive conditions. nNOS inhibition by infusion of Nω-propyl-L-arginine (NPLA) prevents fear-like reactions (e.g., jumping, running, freezing) induced by NMDA receptor stimulation within the dPAG and produces anti-aversive effects when injected into the same midbrain site in mice confronted with a predator. Interestingly, nNOS inhibition within the dPAG does not change anxiety-like behavior in mice exposed to the elevated plus maze (EPM), but it reverses the effect of an anxiogenic dose of NMDA injected into the same site in animals subjected to the EPM. Altogether, the results support a role for glutamate NMDA receptors and NO in the dPAG in the regulation of defensive behaviors in mice. However, dPAG nitrergic modulation of anxiety-like behavior appears to depend on the magnitude of the aversive stimulus.

Recentes evidências têm mostrado que a exposição de camundongos ao labirinto em cruz elevado (LCE), um modelo animal de ansiedade, resulta na exibição de analgesia. Com o objetivo de investigar quais as estruturas que são ativadas durante a exposição ao LCE, no presente estudo foi utilizada a técnica de imunocitoquímica para marcação de proteína Fos em camundongos que receberam injeção intraperitoneal de salina ou ácido acético 0,6% (estímulo nociceptivo) e que foram confinados no braço aberto (situação ameaçadora) ou fechado (controle) do LCE. As seguintes estruturas foram estudadas: núcleos magno, dorsal e mediano da rafe (MR, DR e MnR), matéria cinzenta periaquedutal (PAG), hipocampo ventral e dorsal (DH e VH), amigdala (AMY), hipotálamo (HYP) e colículos superior e inferior (SC e IC). Após quatro dias de manipulação [a manipulação foi conduzida pelo manuseio diário dos animais durante um período de 10 minutos seguidos da injeção i.p. de salina (0,1 mL/10 g)], camundongos receberam injeção i.p. de ácido acético 0,6% ou salina e foram confinados nos braços aberto ou fechado do LCE. Os resultados revelaram que o confinamento no braço aberto aumentou o número de células positivas para Fos no MnR, PAG e IC, indicando que o medo produzido pela ameaça dos braços abertos é modulado por essas estruturas. Embora a análise não tenha revelado efeito para o fator nocicepção (isto é, nenhum efeito do ácido acético) um incremento na expressão de Fos foi registrado somente em animais tratados com ácido acético i.p., sugerindo que a presença simultânea da nocicepção pode estar relacionada ao aumento do recrutamento de neurônios nessas estruturas mesencefálicas.

It has been demonstrated that mice exhibit antinociception when they are exposed to the elevated plus-maze (EPM), an animal model of anxiety. To investigate which brain structures are activated during EPM exposure, the present study assessed the immunohistochemical staining for Fos-like immunoreactivity (Fos-LI) in mice intraperitoneally injected with saline or 0.6% acetic acid (which produces nociception) and confined in the open arm (threatening situation) or enclosed arm (control) of the EPM. The following structures were investigated: magnus, dorsal and median raphe nuclei (MR, DR and MnR), periaqueductal gray matter (PAG), dorsal and ventral hippocampus (DH and VH), amygdala (AMY), hypothalamus (HYP) and superior and inferior colliculi (SC and IC). After four days of habituation (habituation was conducted by handling the animals daily for a period of 10 minutes followed by i.p. injection of saline 0.1 mL/10 g), mice received i.p. injection of 0.6% acetic acid or saline and were confined in open or enclosed arms of the EPM. Results showed that open arm confinement increased the number of positive cells for Fos in MnR, PAG and IC, indicating that the fear produced by the threat of the open arms is modulated by these structures. Although statistical analyses did not reveal any effect for nociception factor, (i.e. no effect of acetic acid) the increase in Fos expression was recorded only in animals treated with i.p. acetic acid, suggesting that the simultaneous presence of nociception could be related to an enhanced recruitment of neurons in those midbrains structures.