Mineralocorticoid receptor-mediated enhancement of neuronal excitability and synaptic plasticity in the dentate gyrus in vivo is dependent on the beta-adrenergic activity.
The dentate gyrus neurons in the hippocampus contain a high density of both mineralocorticoid and adrenergic receptors. By in vivo extracellular recording from adrenalectomized rats we investigated the possible relationships between the two systems with regard to neuronal excitability and activity-dependent synaptic plasticity. Pretreatment with aldosterone significantly enhanced both basal neuronal excitability and tetanically evoked synaptic plasticity in adrenalectomized, but not sham-operated rats. The enhancement was blocked by spironolactone, indicating a mineralocorticoid receptor-dependent effect. The adrenomedullary hormone epinephrine also significantly enhanced synaptic plasticity via activation of beta-adrenergic receptors. Beta-adrenergic antagonist propranolol, infused directly into the dentate gyrus granule cell layer, significantly reduced the effect of aldosterone on neuronal excitability and partly canceled the aldosterone-enhanced synaptic plasticity. No effect of propranolol was found after its amygdaloid infusion. The mineralocorticoid receptor antagonist spironolactone did not affect the epinephrine-induced effects. These results indicate that the pretreated adrenal steroids interact with the catecholaminergic system in the dentate gyrus of adrenalectomized rats and that the functional beta-adrenergic pathway is involved in the mechanism of mineralocorticoid-induced cellular effects in vivo.
Smriga
M
M
Laboratory of Chemical Pharmacology, Graduate School of Pharmaceutical Sciences, University of Tokyo, Japan.
Nishiyama
N
N
Saito
H
H
D000315:Adrenalectomy; D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000318:Adrenergic beta-Agonists / Q000494:pharmacology; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000450:Aldosterone / Q000494:pharmacology; D000818:Animals; D018891:Dentate Gyrus / Q000737:chemistry* / Q000502:physiology; D003983:Dibenzylchlorethamine / Q000494:pharmacology; D004837:Epinephrine / Q000494:pharmacology; D005071:Evoked Potentials / Q000187:drug effects; D008297:Male; D000451:Mineralocorticoid Receptor Antagonists / Q000494:pharmacology; D009473:Neuronal Plasticity / Q000502:physiology*; D009474:Neurons / Q000737:chemistry* / Q000187:drug effects / Q000502:physiology; D011433:Propranolol / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D011943:Receptors, Adrenergic, beta / Q000378:metabolism*; D018161:Receptors, Mineralocorticoid / Q000378:metabolism*; D013148:Spironolactone / Q000494:pharmacology; D013268:Stimulation, Chemical
D000317:Adrenergic alpha-Antagonists; D000318:Adrenergic beta-Agonists; D000319:Adrenergic beta-Antagonists; D000451:Mineralocorticoid Receptor Antagonists; D011943:Receptors, Adrenergic, beta; D018161:Receptors, Mineralocorticoid; D013148:Spironolactone; D003983:Dibenzylchlorethamine; D000450:Aldosterone; D011433:Propranolol; D004837:Epinephrine