Role of β-Adrenoceptors in Memory Consolidation: β3-Adrenoceptors Act on Glucose Uptake and β2-Adrenoceptors on Glycogenolysis

Abstract

Noradrenaline, acting via b 2 -and b 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 b 3 -rather than b 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 b 3 -AR-mediated memory enhancement 20 min posttraining, whereas inhibition of glycogenolysis interfered with b 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) b 2 -and b 3 -ARs consolidate memory by different mechanisms; b 3 -ARs stimulate central glucose transport, whereas b 2 -ARs stimulate central glycogenolysis.

Norepinephrine: A Neuromodulator That Boosts the Function of Multiple Cell Types to Optimize CNS Performance

“…The same study showed that DAB induced memory impairment at specific times after training can be rescued by application of lactate or of the astrocyte-specific metabolic substrate acetate together with aspartate. These act as a precursor for oxaloacetate, which is needed because acetate alone cannot support pyruvate carboxylation [160, 164]. The glutamate precursor glutamine also rescued DAB induced memory impairments as well as the impairment induced by propranolol or by the glutamine synthetase inhibitor MSO.…”

Memory Processing in the Avian Hippocampus Involves Interactions between β-Adrenoceptors, Glutamate Receptors, and Metabolism

“…The effects of the metabolic inhibitors, 2-DG and DAB, that inhibit memory and glucose that facilitates memory when administered into the IMM (Gibbs and Summers, 2002b;Gibbs et al, 2006aGibbs et al, , 2007 were examined in the hippocampus to compare the temporal parameters in the two brain areas. Glucose (10 nmol/hemisphere) administered up to 15 min after weakly reinforced training facilitated memory consolidation (F (7, 107) ¼ 8.74; po0.001) (Figure 11a).…”

“…The doses for glucose and 2-DG were selected from previous work (Gibbs and Summers, 2002b;Gibbs et al, 2007), and DAB was used at 0.1 nmol/ chick s.c. (Figure 12a). A dose of DAB of 0.3 nmol/chick was required to significantly impair memory (Figure 12a) (DAB, F (3, 52) ¼ 11.54; po0.001).…”

Infralimbic cortex Rho-kinase inhibition causes antidepressant-like activity in rats

“…A day old chick's (35-40 g) intermediate medial mesopallium and medial hyperstriatum ventral are not larger than an adult rat's (290-330 g) infralimbic cortex. However, microinjections into these targets with larger volumes (5 to 10 μl) did not cause tissue damages (Gibbs et al, 2008;Steele et al, 1996). Other examples for larger volumes are as follows; rat lateral ventricle microinjections at 10 μl volume (Wang et al, 2004), rat prefrontal cortex microinjections at 5-6 μl volumes (Sogabe et al, 2013).…”