Impairment of nitric oxide (NO) production, ryanodine receptor (RyR) calcium channel function and adrenoceptor activation have been found to prevent the formation of the long-term memory stage in young chicks trained on a single-trial discrimination avoidance task. The current study investigated whether these three activities were linked, and if so, the sequence of activation. Young chicks were trained using either a strongly or weakly reinforced variant of the single-trial discrimination avoidance task, yielding either a persistent or labile memory trace, respectively. Following strongly reinforced training, retention loss induced by a RyR inhibitor was prevented by a NO donor or noradrenaline (NA). A RyR agonist also prevented retention loss induced by either NO synthase or β1+2-adrenoceptor inhibition. These findings were interpreted to reflect the capacity of NO, RyR-dependent calcium release and NA to modulate memory by preventing retention loss. A second set of studies used weakly reinforced training. Although the administration of a RyR agonist promoted long-term memory formation, this facilitation was compromised in the presence of a β1+2-adrenoceptor antagonist, but not a NO synthase inhibitor. Similarly, the inhibition of RyRs interfered with the facilitation of retention induced by a NO donor, but not NA. These differential findings with weakly reinforced training suggest that NO facilitates memory formation through mechanisms involving RyR-dependent calcium release. The findings also indicate that RyRs may promote memory formation through noradrenergic activation of β2-adrenoceptors. This study demonstrates an intricate role for RyRs underlying memory formation.