Stimulation of α1-adrenoceptors inhibits memory consolidation in the chick

Investigation of the effects of the different adrenoceptor (AR) subtypes in memory formation may reveal discrete actions of noradrenaline in memory modulation and storage mediated through particular AR subtypes. Noradrenaline injected intracerebrally in the chick produced biphasic effects on memory consolidation with enhancement at low doses and inhibition at high doses. We have previously shown that the enhancement by the lower doses of noradrenaline is attributable to actions at β₂- and β₃-adrenoceptors, whereas the inhibitory effect of higher doses is attributable to α₁-adrenoceptors. The present studies show that the inhibition of memory by high doses of noradrenaline is mimicked by the α₁-AR agonist methoxamine, and the dose-response curve is shifted to the right by pretreatment with the α₁-AR antagonist prazosin. α₁-ARs may play a critical role in memory formation in highly stressful situations, when noradrenaline levels are high in particular brain regions. It is not known where the α₁-ARs responsible for the effect on memory are localized. α₁-ARs are found on neurons and astrocytes and in the cerebral vasculature and therefore the action of high doses of noradrenaline via α₁-AR agonists could be via an action at any of these sites. Activation of α₁-adrenoceptors in the intermediate hyperstriatum ventrale in the chick forebrain by the α₁ adrenoceptor agonist methoxamine inhibits the consolidation of memory. Because the same effect is produced by high levels of noradrenaline, it is likely that stimulation of α₁-ARs is the mechanism underlying this effect.