Role of the basolateral amygdala dopamine receptors in arachidonylcyclopropylamide-induced fear learning deficits

There is much evidence suggesting that the mesoamygdala dopaminergic (DAergic) system plays a crucial role in the formation and expression of fear conditioning, with both D1 and D2 receptors being involved. In addition, cannabinoid CB1 receptor (CB1R) signaling modulates DAergic pathways. The present study sought to determine the involvement of basolateral amygdala (BLA) dopamine receptors in arachidonylcyclopropylamide (ACPA)-induced fear learning deficits. Context- and tone-dependent fear conditioning in adult male NMRI mice was evaluated. Pre-training intraperitoneal administration of ACPA (0.1 mg/kg) decreased the percentage of freezing in context- or tone-dependent fear conditioning, suggesting an acquisition impairment. Pre-training intra-BLA microinjection of a subthreshold dose of SKF38393 (D1-like receptor agonist), SCH23390 (D1-like receptor antagonist), quinpirole (D2-like receptor agonist), or sulpiride (D2-like receptor antagonist) did not alter the context-dependent fear learning deficit induced by ACPA, while SKF38393 or quinpirole restored ACPA effect on tone-dependent fear learning. Moreover, SKF38393 (1 μg/mouse), SCH23390 (0.04 and 0.08 μg/mouse), or quinpirole (0.1 μg/mouse) all impaired context-dependent fear learning. It is concluded that D1 or D2 dopamine (DA) receptor activation restores tone- but not context-dependent fear learning deficit induced by CB1 activation using ACPA.