Dose-response effects of systemic anandamide administration in mice sequentially submitted to the open field and elevated plus-maze tests

Abstract

The endocannabinoid system is involved in the control of many physiological functions, including the control of emotional states. In rodents, previous exposure to an open field increases the anxiety-like behavior in the elevated plus-maze. Anxiolytic-like effects of pharmacological compounds that increase endocannabinoid levels have been well documented. However, these effects are more evident in animals with high anxiety levels. Several studies have described characteristic inverted U-shaped dose-response effects of drugs that modulate the endocannabinoid levels. However, there are no studies showing the effects of different doses of exogenous anandamide, an endocannabinoid, in animal models of anxiety. Thus, in the present study, we determined the dose-response effects of exogenous anandamide at doses of 0.01, 0.1, and 1.0 mg/kg in C57BL/6 mice (N = 10/ group) sequentially submitted to the open field and elevated plus-maze. Anandamide was diluted in 0.9% saline, ethyl alcohol, Emulphor ® (18:1:1) and administered ip (0.1 mL/10 g body weight); control animals received the same volume of anandamide vehicle. Anandamide at the dose of 0.1 mg/kg (but not of 0.01 or 1 mg/kg) increased (P < 0.05) the time spent and the distance covered in the central zone of the open field, as well as the exploration of the open arms of the elevated plus-maze. Thus, exogenous anandamide, like pharmacological compounds that increase endocannabinoid levels, promoted a characteristic inverted U-shaped dose-response effect in animal models of anxiety. Furthermore, anandamide (0.1 mg/kg) induced an anxiolytic-like effect in the elevated plus-maze (P < 0.05) after exposing the animals to the open field test.

Differential behavioral outcomes of 3,4-methylenedioxymethamphetamine (MDMA-ecstasy) in anxiety-like responses in mice

“…Thus, mice were treated with MDMA and first analyzed in the open field and later in the elevated plus maze. Previous results from our group and others have shown that testing animals in an open field or in a hole board immediately before the elevated plus-maze test significantly elevates animal activity within this apparatus, i.e., the total number of open-and closed-arm entries (13,14), with a consequent simplification of analysis of the elevated plus-maze data. We also tested MDMA-treated mice in the hole-board test, since it has been indicated that head-dipping behavior is sensitive to changes in the emotional state of the animal, and the expression of an anxiolytic-like state in animals might be reflected by an increase in frequency and time of head-dipping (15).…”

Anandamide Reduces the Ejaculatory Threshold of Sexually Sluggish Male Rats: Possible Relevance for Human Lifelong Delayed Ejaculation Disorder

“…or its vehicle on sexual behavior display. AEA doses were chosen based on published data showing facilitative actions of this endocannabinoid on behavioral responses [10–12]. Five additional groups were used to test the effects of different doses the CB1 receptor antagonist AM251 (0.1–3.0 mg/kg) or its vehicle on copulatory behavior of SLG males.…”

Ativação de receptores nicotínicos modula a atividade de células dendríticas OVA sensibilizadas

“…Desta forma, podemos citar algumas formas de ligação entre o SNC e o sistema imune como: o sistema endócrino, em especial, o eixo Hipotálamo Pituitária Adrenal (HPA) (Ader, 2007;Cohen e Herbert, 1996;Conti, 2000;Dunn, 1995); o Sistema Nervoso Autônomo (SNA) (Blalock, 1994); e também a própria atividade neural uma vez que medicamentos de ação central, como o diazepam (Lazzarini et al, 2006;Lazzarini et al, 2001;Sakai et al, 2006a;Sakai et al, 2006b), os endocanabinóides (Ribeiro et al, 2009;Ribeiro et al, 2010) e psicoestimulantes, entre eles a anfetamina (Ligeiro-Oliveira et al, 2004;Ligeiro de Oliveira et al, 2008; A ativação do eixo HPA, e a conseqüente produção dos glicocorticóides, durante o estresse é um dos principais mecanismos responsáveis pelas alterações encontradas no decorrer de uma resposta imune. Sabe-se serem os glicocorticóides capazes de: inibir a transcrição de genes para inúmeras citocinas, como aqueles para interleucina (IL) 1, IL-6, IL-8, IL-11, IL-12, IL-13, IL-16, fator de necrose tumoral (TNF), interferon γ (IFNγ) (Ader, 2007); interferir negativamente com o desenvolvimento e migração de células T através de uma inibição da expressão de moléculas de adesão (Schoneveld, 2007); diminuir a atividade de macrófagos (Massoco e Palermo-Neto, 2003); e reduzir a atividade de neutrófilos (Alves et al, 2006).…”