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 (C SF) of freely-moving rats that had been administered citalopram, +/- 1 -[3-(Dimethylamino)propyl]-1-(4-fluorophentyl)-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 administerd. The 5-HT concentrations in CSF from the cisterna magna increased significantly, reaching a maximum 6 hours aft er a single dose of citalopram (30 mg/kg p.o.) was given. Six hours af ter this dose, the CSF 5-HT concentration in the cisterna magna was si gnificantly increased, and the 5-hydroxyindoleacetic acid (5-HIAA) con centration was significantly decreased. There were non-significant cha nges in the other indoleamines (tryptophan, 5-hydroxytryptophan, and k ynurenine) and in the catecholamines (dopamine, homovanillic acid, nor metanephrine, and 3-methoxy-4-hydroxyphenethyleneglycol). The 5-HT/try ptophan ratio was correlated significantly with the kynurenine/tryptop han ratio before treatment with citalopram (r = 0.81, p = 0.051), indi cative that there is coordination of the serotonin and kynurenine path ways in normal rats. In the animals posttreatment there was no such co rrelation, 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 catechol amines.