Resumo

Endocannabinoids modulate a variety of brain functions via activation of CB1 receptors, widely expressed in the brain, with special density in the basolateral amygdala (BLA), structure involved in the consolidation of aversive memories. Systemic activation and blockage of CB1 receptor has been shown to modify memory processing, as well as emotional states, however little is known about the role of BLA CB1 receptors in aversive memory. In this study, the role of the endocannabinoid transmission in the BLA during acquisition of aversive memories, and its modulation of anxiety levels were simultaneously investigated in rats. Male Wistar rats (250-300g) were implanted with bilateral cannula aimed at the basolateral amygdala (BLA) and assigned to one of three different groups, that received infusions of: (I) vehicle DMSO4 8%; (II) CB1 antagonist AM251 (10ng/site); or (III) CB1 agonist anandamide (1ng/site). Fifteen minutes after infusion, animals were submitted to the training session of the plus-maze discriminative avoidance task. The apparatus employed has two open arms and two enclosed arms, one of which presenting aversive stimuli (light - 1920lux and noise - 80dB). During training session (10 min), the aversive stimuli are given immediately after the rat entered the aversive arm, lasting until the animal leaves it. During test, the stimuli were no longer applied. In both sessions, the time spent in the open arms, aversive enclosed arm and non-aversive enclosed arm were measured and compared by two-way ANOVA followed by Bonferroni’s test. Our results showed that the three groups learned the task, i.e. showed a reduction of the percent time in the aversive arm during training session, with no significant differences regarding neither locomotion nor anxiety. In contrast, the pre-training infusion of anandamide into the BLA impaired memory retrieval, assessed by the percent time spent in the aversive arm (control 27.82±4.49; anandamide 59.65±7.49; F(2, 16)= 8.547; P < 0.01), as well as habituation, evaluated by traveled distance (control 14.59±2.33; anandamide 24.54±3.74; t test P < 0.04), both during test session, suggesting a widespread memory impairment. The infusion of AM251 did not show any effect compared to control group. Altogether, these results suggest that the endocannabinoid transmission in BLA may not act specifically on the acquisition of aversive memories, but on the processing of recently acquired information. Therefore, further studies are needed to ensure that these differences due to pre-training infusion, but seen only in memory retrieval, are related to post-training effects of the drugs in the modulation of aversive memory consolidation.