Bidirectional influence of amygdala β 1 -adrenoceptors blockade on cannabinoid signaling in contextual and auditory fear memory

Abstract

The basolateral amygdala (BLA) is a major target and modulator of stress and has a critical role in the neural circuitry presenting learned fear behaviors. On the other hand, both the endocannabinoid and noradrenergic systems may be involved in regulating the stress responses, fear, and anxiety. Considering the aforementioned, we have investigated the involvement of the BLA β₁-adrenoceptors in conditioned fear responses induced by ACPA, a CB1 receptor (CB1R) agonist. In adult male NMRI mice, freezing responses to context and cue were measured using a Pavlovian fear conditioning apparatus. Pre-training intra-BLA microinjection of xamoterol (0.01 and 0.02 µg/mouse), a partial β₁-adrenoceptor agonist, or atenolol (0.5 µg/mouse), a β₁-adrenoceptor antagonist, decreased freezing behavior, which suggests an impairment of contextual and auditory fear retrieval. Similar results were found with pre-training intraperitoneal administration of ACPA (0.5 mg/kg). A sub-threshold dose of xamoterol, infused into the BLA, decreased ACPA (0.005 and 0.05 mg/kg) effect on both memories, while atenolol increased ACPA response to the context at the middle dose and decreased ACPA response to the tone at the lower dose. It can be concluded that the blockade of BLA β₁-adrenoceptors differentially affects ACPA response on the contextual and auditory conditioned fear memories.