Inhibitory effects of clonidine on serotonergic neuronal activity as measured by cerebrospinal fluid serotonin and its metabolite in anesthetized rats.
Clonidine-induced changes in the serotonergic neuronal activity of the central nervous system were estimated by measuring the concentrations of serotonin (5-HT) and its major metabolite, 5-hydroxyindole-3-acetic acid (5-HIAA), in the cerebrospinal fluid (CSF) of anesthetized rats. Clonidine (30 and 300 micrograms/kg, i.v.) led to 74% and 60% reductions in the concentration of 5-HT in the CSF 60 min after administration. CSF 5-HIAA concentrations were also decreased to 77% and 66%, respectively. Clonidine-induced (30 micrograms/kg, i.v.) decreases in CSF 5-HT and 5-HIAA concentrations were attenuated by pretreatment with idazoxan (5 mg/kg, i.p.). Idazoxan by itself did not alter the CSF 5-HT and 5-HIAA concentrations. Decreased CSF 5-HT and 5-HIAA concentrations after i.v. administration of clonidine (30 micrograms/kg) were abolished by noradrenergic denervation after pretreatment with 6-hydroxydopamine (200 micrograms/rat, i.c.v.). These results suggest the possibility that clonidine acts to inhibit the serotonergic neuronal activity, which is mediated via the alpha 2-adrenoceptors. It indicates, moreover, that noradrenergic nervous systems are involved in the clonidine-induced inhibition of serotonergic neuronal activity. Therefore, noradrenergic neurons play a significant role in mediating the actions of clonidine on serotonergic neuronal activity in the rat brain.
Matsumoto
M
M
First Department of Pharmacology, Hokkaido University School of Medicine, Sapporo, Japan.
Togashi
H
H
Yoshioka
M
M
Hirokami
M
M
Tochihara
M
M
Ikeda
T
T
Smith
C B
CB
Saito
H
H
D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000818:Animals; D002490:Central Nervous System / Q000187:drug effects*; D002851:Chromatography, High Pressure Liquid; D003000:Clonidine / Q000494:pharmacology*; D004146:Dioxanes / Q000494:pharmacology; D019329:Idazoxan; D008297:Male; D016627:Oxidopamine / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D012701:Serotonin / Q000031:analogs & derivatives / Q000134:cerebrospinal fluid*; D012702:Serotonin Antagonists / Q000494:pharmacology
D000317:Adrenergic alpha-Antagonists; D004146:Dioxanes; D012702:Serotonin Antagonists; D012701:Serotonin; D016627:Oxidopamine; D003000:Clonidine; D019329:Idazoxan