Separate roles for beta2- and beta3-adrenoceptors in memory consolidation.
Consolidation of a labile memory which would not normally be stored can be achieved by intracerebral administration of noradrenaline. In a series of experiments using discriminated, one trial passive avoidance learning with the day-old chick, the effect of noradrenaline has been shown to be due to actions at different subtypes of adrenoceptors. The effect of noradrenaline is dose-dependent, with a moderate dose producing memory consolidation. However, higher doses of noradrenaline (0.3-10 nmol/hemisphere) prevent consolidation, an effect not seen with isoprenaline suggesting that these doses stimulate alpha-adrenoceptors. The promotion of memory consolidation by noradrenaline or isoprenaline at low doses was attributable to beta3-adrenoceptors and at medium doses to beta2-adrenoceptors. At higher doses of noradrenaline, there was alpha1-adrenoceptor-mediated inhibition of memory consolidation. Consolidation can also be achieved by administration of either beta2- or beta3-adrenoceptor agonists at specific times after training. Although these two adrenoceptors both promoted memory consolidation, there was a differential action on the stages of memory formation. The dose-response curve to the beta3- and the beta2-agonists was shifted by the appropriate antagonist but not by the antagonist at the other beta-adrenoceptor. Although beta1-adrenoceptors are present in chick brain, they do not seem to have a role in memory formation. These results explain why noradrenaline, acting at different adrenoceptors, can have different effects on memory formation with memory being either consolidated or inhibited depending on the dose. The findings also demonstrate a role in memory formation for beta3-adrenoceptors found in the brain. Agonists acting specifically at beta2- or beta3-adrenoceptors may be of value in diseases involving cognitive impairment.
Gibbs
M E
ME
Department of Psychology, Monash University, Clayton, Australia.
Summers
R J
RJ
D000318:Adrenergic beta-Agonists / Q000494:pharmacology; D000818:Animals; D000831:Animals, Newborn / Q000502:physiology / Q000523:psychology; D001362:Avoidance Learning / Q000502:physiology; D001921:Brain / Q000502:physiology; D002395:Catecholamines / Q000502:physiology; D002645:Chickens; D004149:Dioxoles / Q000494:pharmacology; D004983:Ethanolamines / Q000494:pharmacology; D007267:Injections; D007545:Isoproterenol / Q000494:pharmacology; D008297:Male; D008568:Memory / Q000187:drug effects / Q000502:physiology*; D020033:Protein Isoforms / Q000502:physiology; D011943:Receptors, Adrenergic, beta / Q000502:physiology*
D000318:Adrenergic beta-Agonists; D002395:Catecholamines; D004149:Dioxoles; D004983:Ethanolamines; D020033:Protein Isoforms; D011943:Receptors, Adrenergic, beta; C076126:disodium (R,R)-5-(2-((2-(3-chlorophenyl)-2-hydroxyethyl)-amino)propyl)-1,3-benzodioxole-2,3-dicarboxylate; C002904:zinterol; D007545:Isoproterenol