Role of beta-adrenoceptors in memory consolidation: beta3-adrenoceptors act on glucose uptake and beta2-adrenoceptors on glycogenolysis.
Noradrenaline, acting via beta(2)- and beta(3)-adrenoceptors (AR), enhances memory formation in single trial-discriminated avoidance learning in day-old chicks by mechanisms involving changes in metabolism of glucose and/or glycogen. Earlier studies of memory consolidation in chicks implicated beta(3)- rather than beta(2)-ARs in enhancement of memory consolidation by glucose, but did not elucidate whether stimulation of glucose uptake or of glycolysis was responsible. This study examines the role of glucose transport in memory formation using central injection of the nonselective facilitative glucose transporter (GLUT) inhibitor cytochalasin B, the endothelial/astrocytic GLUT-1 inhibitor phloretin and the Na(+)/energy-dependent endothelial glucose transporter (SGLT) inhibitor phlorizin. Cytochalasin B inhibited memory when injected into the mesopallium (avian cortex) either close to or between 25 and 45 min after training, whereas phloretin and phlorizin only inhibited memory at 30 min. This suggested that astrocytic/endothelial (GLUT-1) transport is critical at the time of consolidation, whereas a different transporter, probably the neuronal glucose transporter (GLUT-3), is important at the time of training. Inhibition of glucose transport by cytochalasin B, phloretin, or phlorizin also interfered with beta(3)-AR-mediated memory enhancement 20 min posttraining, whereas inhibition of glycogenolysis interfered with beta(2)-AR agonist enhancement of memory. We conclude that in astrocytes (1) activities of both GLUT-1 and SGLT are essential for memory consolidation 30 min posttraining; (2) neuronal GLUT-3 is essential at the time of training; and (3) beta(2)- and beta(3)-ARs consolidate memory by different mechanisms; beta(3)-ARs stimulate central glucose transport, whereas beta(2)-ARs stimulate central glycogenolysis.
Department of Anatomy and Developmental Biology, Monash University, Australia. marie.gibbs@med.monash.edu.au
Marie E
ME
Gibbs
Dana S
DS
Hutchinson
Roger J
RJ
Summers
D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism*; D001923:Brain Chemistry / Q000187:drug effects / Q000502:physiology; D002645:Chickens; D003571:Cytochalasin B / Q000494:pharmacology; D005947:Glucose / Q000378:metabolism*; D051246:Glucose Transport Proteins, Facilitative / Q000037:antagonists & inhibitors / Q000378:metabolism; D051272:Glucose Transporter Type 1 / Q000037:antagonists & inhibitors / Q000378:metabolism; D051274:Glucose Transporter Type 3 / Q000037:antagonists & inhibitors / Q000378:metabolism; D006003:Glycogen / Q000378:metabolism; D050261:Glycogenolysis / Q000187:drug effects / Q000502:physiology*; D007858:Learning / Q000187:drug effects / Q000502:physiology; D008297:Male; D008568:Memory / Q000187:drug effects / Q000502:physiology*; D009638:Norepinephrine / Q000378:metabolism; D010693:Phloretin / Q000494:pharmacology; D010695:Phlorhizin / Q000494:pharmacology; D018343:Receptors, Adrenergic, beta-2 / Q000187:drug effects / Q000378:metabolism*; D022702:Receptors, Adrenergic, beta-3 / Q000187:drug effects / Q000378:metabolism*; D051247:Sodium-Glucose Transport Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism
D051246:Glucose Transport Proteins, Facilitative; D051272:Glucose Transporter Type 1; D051274:Glucose Transporter Type 3; D018343:Receptors, Adrenergic, beta-2; D022702:Receptors, Adrenergic, beta-3; D051247:Sodium-Glucose Transport Proteins; D003571:Cytochalasin B; D006003:Glycogen; D010695:Phlorhizin; D005947:Glucose; D010693:Phloretin; D009638:Norepinephrine