Stimulation of alpha1-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 beta2- and beta3-adrenoceptors, whereas the inhibitory effect of higher doses is attributable to alpha1-adrenoceptors. The present studies show that the inhibition of memory by high doses of noradrenaline is mimicked by the alpha1-AR agonist methoxamine, and the dose-response curve is shifted to the right by pretreatment with the alpha1-AR antagonist prazosin. alpha1-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 alpha1-ARs responsible for the effect on memory are localized. alpha1-ARs are found on neurons and astrocytes and in the cerebral vasculature and therefore the action of high doses of noradrenaline via alpha1-AR agonists could be via an action at any of these sites. Activation of alpha1-adrenoceptors in the intermediate hyperstriatum ventrale in the chick forebrain by the alpha1 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 alpha1-ARs is the mechanism underlying this effect.
Gibbs
M E
ME
Department of Pharmacology, Monash University, Clayton, 3800 Australia. marie.gibbs@med.monash.edu.au
Summers
R J
RJ
D058646:Adrenergic alpha-1 Receptor Agonists; D000316:Adrenergic alpha-Agonists / Q000494:pharmacology; D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology; D002645:Chickens / Q000378:metabolism*; D004193:Discrimination Learning / Q000187:drug effects / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D004347:Drug Interactions / Q000502:physiology; D019332:Endothelin-1 / Q000494:pharmacology; D008568:Memory / Q000187:drug effects / Q000502:physiology*; D008569:Memory Disorders / Q000139:chemically induced / Q000378:metabolism / Q000503:physiopathology; D008729:Methoxamine / Q000494:pharmacology; D009638:Norepinephrine / Q000819:agonists / Q000378:metabolism*; D011224:Prazosin / Q000494:pharmacology; D016548:Prosencephalon / Q000187:drug effects / Q000378:metabolism*; D018340:Receptors, Adrenergic, alpha-1 / Q000378:metabolism*; D062367:ortho-Aminobenzoates / Q000494:pharmacology
D058646:Adrenergic alpha-1 Receptor Agonists; D000316:Adrenergic alpha-Agonists; D000317:Adrenergic alpha-Antagonists; D000927:Anticonvulsants; D019332:Endothelin-1; D018340:Receptors, Adrenergic, alpha-1; D062367:ortho-Aminobenzoates; C031385:anthranilic acid; D008729:Methoxamine; D009638:Norepinephrine; D011224:Prazosin