Effects of citalopram, a synthetic serotonin uptake inhibitor, on indoleamine and catecholamine concentrations in the cerebrospinal fluid of freely moving rats.
We studied changes in the concentrations of 5-hydroxytryptamine (5-HT), other indoleamines, and catecholamines in the cerebrospinal fluid (CSF) of freely-moving rats that had been administered citalopram, +/-1-[3- (Dimethylamino)propyl)-1-(4-fluorophenyl)-1, 3-dihydro-5-isobenzo-furancarbonitrile hydrobromide), a selective inhibitor of 5-HT uptake. In a microdialysis experiment, the intracerebral extracellular free 5-HT increased significantly, peaking 60 to 90 min after citalopram (30 mg/kg p.o.) was administered. The 5-HT concentrations in CSF from the cisterna magna increased significantly, reaching a maximum 6 hours after a single dose of citalopram (30 mg/kg p.o.) was given. Six hours after this dose, the CSF 5-HT concentration in the cisterna magna was significantly increased, and the 5-hydroxyindoleacetic acid (5-HIAA) concentration was significantly decreased. There were non-significant changes in the other indoleamines (tryptophan, 5-hydroxytryptophan, and kynurenine) and in the catecholamines (dopamine, homovanillic acid, normetanephrine, and 3-methoxy-4-hydroxyphenethyleneglycol). The 5-HT/tryptophan ratio was correlated significantly with the kynurenine/tryptophan ratio before treatment with citalopram (r = 0.81, p = 0.051), indicative that there is coordination of the serotonin and kynurenine pathways in normal rats. In the animals posttreatment there was no such correlation, suggesting that the changes in 5-HT are independent of the kynurenine system at least within the 6 hours postreatment. These CSF results appear to reflect selective inhibition of 5-HT uptake in brain tissues by citalopram that is not associated with changes in catecholamines.
Tohgi
H
H
Department of Neurology, Iwate Medical University, Morioka, Japan.
Abe
T
T
Nakanishi
M
M
Takahashi
S
S
Furuichi
H
H
Matsumura
T
T
Kurimoto
T
T
Izumi
J
J
Ikeda
Y
Y
D000818:Animals; D002395:Catecholamines / Q000134:cerebrospinal fluid*; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism; D002946:Cisterna Magna / Q000378:metabolism; D015283:Citalopram / Q000493:pharmacokinetics / Q000494:pharmacology*; D007211:Indoles / Q000134:cerebrospinal fluid*; D007737:Kynurenine / Q000378:metabolism; D008297:Male; D017551:Microdialysis; D051381:Rats; D011916:Rats, Inbred F344; D017208:Rats, Wistar; D012701:Serotonin / Q000378:metabolism; D017367:Selective Serotonin Reuptake Inhibitors / Q000493:pharmacokinetics / Q000494:pharmacology*
D002395:Catecholamines; D015283:Citalopram; D007211:Indoles; D007737:Kynurenine; D012701:Serotonin; D017367:Selective Serotonin Reuptake Inhibitors