Efeito do canabidiol no comportamento tipo ansioso e na formação de mememória aversiva em ratas

Abstract

Anxiety is an adaptive state that causes defensive behavior in the face of unfamiliar or potentially dangerous situations, which can lead to pathological conditions. Studies show that anxiety is more prevalent in women and may be related to hormonal fluctuations during the menstrual cycle. However, in women, the treatment of anxiety with anxiolytics has low efficiency and many adverse effects, so new compounds have been studied for the treatment of anxiety. One of these is cannabidiol (CBD), which has shown therapeutic potential for emotional and psychological problems. The aim of this study was to evaluate the effect of cannabidiol on anxiety-like behavior and the formation of aversive memory in female rats. Forty-two three-month-old Wistar female rats were divided into three groups: control (CTR), treated with 0.9% NaCl saline, diazepan (DZP) 2.0mg/kg and cannabidiol (CBD) 0.3mg/kg. The rats' estrous cycle was monitored for 10 days to confirm the phases of the estrous cycle and the experiment took place in the late diestrus phase. After confirmation, the rats received an intraperitoneal injection according to the experimental groups, respectively. 1 hour after the injection, the animals were submitted to the modified elevated cross maze and, 1 hour after the test, they were anesthetized, sacrificed and the brains collected and submitted to immunohistochemistry for c-Fos. We observed that the DZP and CBD groups showed reduced anxiety and only the DZP group showed impaired memory formation. In the analysis of c-Fos immunoreactivity, we observed a reduction in the number of c-Fos+ cells for the CBD and DZP groups in the dorsomedial paraqueductal gray matter (PAG) (p<0.05), hippocampus (p<0.05) and hypothalamus (p<0.05), when compared to the CTR. However, in the ventromedial PAG there was an increase in c-Fos+ cells for the CBD (p<0.05) and DZP (p<0.05) groups, compared to the CTR. CBD caused a reduction in c-Fos+ in the locus coeruleus (p<0.05) and an increase in the bed nucleos of the stria terminalis (p<0.05) compared to the other groups. In the amygdala, the DZP group showed a reduction in c-Fos+ compared to the other groups. Thus, our data suggest that acute treatment with CBD has an anxiolytic effect without impairing the memory of female rats in the late diestrus phase, as it involves the action of different brain areas.