Serotonin does not mediate the adrenal catecholamine-releasing effect of acute lithium administration in rats.
The activity of central serotonin (5-hydroxytryptamine, 5-HT) systems has been reported to be affected by repeated, and to a lesser extent by acute, lithium chloride (LiCl) treatment. Because (1) acute LiCl administration increases sympathoadrenal function, and in turn plasma glucose levels, and (2) stimulation of either the 5-HT1A, the 5-HT1C or the 5-HT2 receptor subtype has adrenal catecholamine-releasing and hyperglycemic effects, we have investigated the influence of prior blockade of either of these receptor subtypes on plasma catecholamine and glucose responses to acute LiCl administration in conscious, catheterized rats. Acute administration of LiCl (1-8 mEq/kg IV) triggered dose-dependent increases in plasma epinephrine (Epi), norepinephrine (NE), and glucose levels throughout the 60-min analysis. In contrast, administration of NaCl (8 mEq/kg IV) did not alter plasma Epi or NE levels, nor did it affect plasma glucose levels. Prior blockade of 5-HT1A receptor and beta-adrenoceptors by means of (-)-propranolol (5 mg/kg IV), 10 min beforehand) did not affect plasma Epi and NE responses to LiCl (4 mEq/kg), but it did prevent the hyperglycemic effect of LiCl. Plasma Epi, NE and glucose responses to LiCl remained intact in rats pretreated with the 5-HT1C/5-HT2 receptor antagonist LY 53857 (1 mg/kg IV), 10 min beforehand). These results strongly suggest that LiCl-induced adrenal catecholamine release (and hyperglycemia) is not mediated by increased 5-HT release.
Chaouloff
F
F
Department of Medicine, Harvard Medical School, Boston, Massachusetts.
Gunn
S H
SH
Young
J B
JB
D000311:Adrenal Glands / Q000187:drug effects* / Q000502:physiology; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D001921:Brain / Q000187:drug effects* / Q000502:physiology; D002712:Chlorides / Q000494:pharmacology*; D004837:Epinephrine / Q000097:blood*; D004873:Ergolines / Q000494:pharmacology; D008094:Lithium / Q000494:pharmacology*; D018021:Lithium Chloride; D008297:Male; D009638:Norepinephrine / Q000097:blood*; D011433:Propranolol / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D011985:Receptors, Serotonin / Q000187:drug effects* / Q000502:physiology; D012701:Serotonin / Q000502:physiology*; D012702:Serotonin Antagonists / Q000494:pharmacology
D001786:Blood Glucose; D002712:Chlorides; D004873:Ergolines; D011985:Receptors, Serotonin; D012702:Serotonin Antagonists; D012701:Serotonin; D008094:Lithium; D011433:Propranolol; D018021:Lithium Chloride; C032663:LY 53857; D009638:Norepinephrine; D004837:Epinephrine