Pharmacobehavioural evidence for nitric oxide and noradrenaline interactions with ryanodine receptors during memory formation in the young chick

Behav Neurosci. 2011 Apr;125(2):175-83. doi: 10.1037/a0022537.


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.

Publication types

  • Comparative Study

MeSH terms

  • Age Factors
  • Animals
  • Animals, Newborn
  • Avoidance Learning / drug effects
  • Avoidance Learning / physiology
  • Chickens
  • Dantrolene / metabolism
  • Dantrolene / pharmacology
  • Memory / physiology*
  • NG-Nitroarginine Methyl Ester / metabolism
  • NG-Nitroarginine Methyl Ester / pharmacology
  • Nitric Oxide / agonists
  • Nitric Oxide / antagonists & inhibitors
  • Nitric Oxide / metabolism*
  • Nitric Oxide Donors / metabolism
  • Nitric Oxide Donors / pharmacology
  • Norepinephrine / metabolism*
  • Propranolol / metabolism
  • Propranolol / pharmacology
  • Ryanodine Receptor Calcium Release Channel / metabolism*


  • Nitric Oxide Donors
  • Ryanodine Receptor Calcium Release Channel
  • Nitric Oxide
  • Propranolol
  • Dantrolene
  • NG-Nitroarginine Methyl Ester
  • Norepinephrine