Role of the amygdala GABA-A receptors in ACPA-induced deficits during conditioned fear learning

Abstract

The basolateral amygdala (BLA) is a key structure for the emotional processing and storage of memories associated with emotional events, especially fear. On the other hand, endocannabinoids and CB1 receptors play a key role in learning and memory partly through long-term synaptic depression of GABAergic synapses in the BLA. The aim of this study was to explore the effects of GABA-A receptor agonist and antagonist in the fear-related memory acquisition deficits induced by ACPA (a selective CB1 cannabinoid receptor agonist). This study used context and tone fear conditioning paradigms to assess fear-related memory in male NMRI mice. Our results showed that the pre-training intraperitoneal administration of ACPA (0.5mg/kg) or (0.1 and 0.5mg/kg) decreased the percentage of freezing time in the contextual and tone fear conditioning, respectively. This indicated an impaired context- or tone-dependent fear memory acquisition. Moreover, the pre-training intra-BLA microinjection of GABA-A receptor agonist, muscimol, at 0.05 and 0.5μg/mouse impaired context-dependent fear memory, while the same doses of GABA-A antagonist, bicuculline, impaired tone-dependent fear memory. However, a subthreshold dose of muscimol or bicuculline increased the effect of ACPA at 0.1 and 0.5 or 0.05mg/kg on context- or tone-dependent fear memory, respectively. In addition, bicuculline at the lower dose increased the ACPA response on locomotor activity compared to its respective group. Such findings highlighted an interaction between BLA GABAergic and cannabinoidergic systems during the acquisition phase of conditioned fear memories.

Involvement of Epigenetic Modifications of GABAergic Interneurons in Basolateral Amygdala in Anxiety-like Phenotype of Prenatally Stressed Mice

“…Cannulae were implanted with bilateral 27-gauge stainless steel cannulas into the bilateral BLA ( Figure 1 ) according to the mouse brain in stereotaxic coordinates ( Paxinos and Franklin, 2001 ). After a 7-day recovery period, animals received bilateral injection of the drugs with 0.3 μL/side through the infusion cannula ( Nasehi et al, 2017 ). 5-Aza-deoxycytidine (5-aza-CdR; A3656; Sigma-Aldrich) was dissolved in 0.8% acetate and diluted to a concentration of 200 ng/μL in saline.…”

Endocannabinoid metabolism inhibition has no effect on spontaneous fear recovery or extinction resistance in Lister hooded rats

“…CB1R activation by elevated AEA or 2-AG levels may, therefore, have potentiated this interoceptive state or its contextual association. Although the findings from previous studies on CB1R regulation of contextual fear conditioning are mixed ( Pamplona and Takahashi, 2006 ; Arenos et al, 2006 ; Butler et al, 2008 , 2012 ; Jacob et al, 2012 ; Laricchiuta et al, 2013 ; Hartley et al, 2016 ; Nasehi et al, 2017 ; Balogh et al, 2019 ; Kondev et al, 2022 ), there is emerging evidence supporting a role for CB1R signalling in regulating negative interoceptive states ( Andrade et al, 2019 ). Another possibility is that URB597 and JZL184 resulted in contextual fear generalization, although there is less support for this idea ( Reich et al, 2008 ).…”

The dorsal subiculum is not necessary for step-through inhibitory avoidance acquisition and consolidation in rats.

“…The animals were regularly manipulated in the 4 days before the beginning of the behavioral experiment to habituate them to the investigator’s touch and presence and simulate the infusion protocol. On the day of the behavioral experiment, the animals received a bilateral infusion of muscimol (Sigma-Aldrich®) or AP5 (Tocris®) 5 min before the training (Souza & Carobrez, 2016; Nasehi et al, 2017) or immediately after training (Melo et al, 2020) by a technician blinded to the group allocation. The posttraining infusions occurred less than 30 s after the end of the training, which is the time it took to remove the animal from the conditioning chamber and attach the two infusion stylets (one per hemisphere) to the guide cannulas.…”