Interactions between Antimigraine Drugs and a High Affinity Uptake and Storage Mechanism for 5-Hydroxytryptamine

Fozard, John R.; Berry, Jacqueline

doi:10.1159/000136615

Cited by 7 publications

(1 citation statement)

References 5 publications

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“…3 H]5-HT and their respective 3 H-metabolites (Fozard and Berry, 1976). In this study, for convenience, the collected 3 H]5-HT was expressed in absolute values (dpm/5 min) and as a fraction of the amount of radioactivity present in the tissue (slices) at the time of sample collection.…”

Section: Displacement Of Stored [mentioning

confidence: 99%

The Selective Serotonin Reuptake Inhibitor Citalopram Induces the Storage of Serotonin in Catecholaminergic Terminals

Suárez-Roca

Cubeddu²

2002

J Pharmacol Exp Ther

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We investigated whether selective inhibition of serotonin (5-hydroxytryptamine; 5-HT) transporter with citalopram leads to accumulation of 5-HT in catecholaminergic neurons. In the rabbit olfactory tubercle, citalopram (1-10 M) inhibited [3 H]5-HT uptake; however, the maximal degree of inhibition achieved was 70%. Addition of nomifensine (1-10 M) was required for complete inhibition of Despite their lower affinity for serotonin (5-hydroxytryptamine; 5-HT), there is experimental evidence to suggest that catecholaminergic neurons may take up and store 5-HT. Indeed, 5-HT-immunoreactive fibers in the pars intermedia of the rat pituitary gland can be eliminated by treatment with 6-hydroxydopamine, a neurotoxin selective for catecholamine neurons (Saland et al., 1986). Interestingly, Thind and coworkers (1987) observed the presence of 5-HT staining in tyrosine hydroxylase-immunoreactive fibers in the suprachiasmatic nuclei and ventromedial hypothalamus 24 h after infundibular stalk section. These authors proposed that catecholaminergic terminals might take up 5-HT coming from cut 5-HT terminals. In a study by Feuerstein and coworkers (1986), prolonged incubations of caudate nucleus slices with [ 3 H]5-HT led to labeling of catecholaminergic terminals, which was prevented by the NE/DA uptake inhibitor nomifensine but not by the selective 5-HT reuptake inhibitor 6-nitroquipazine. The above observations suggest that storage of 5-HT may occur in catecholamine-containing neurons. Based on the above described findings, we proposed that in brain areas where there is a coexistence of catecholaminergic and serotonergic terminals, 5-HT could accumulate in catecholaminergic neurons if the 5-HT neuronal transporter (neuronal uptake pump) is inhibited with a selective 5-HT transporter inhibitor. To test this hypothesis, we employed the olfactory tubercle of the rabbit because of its high density of 5-HT, DA, and NE terminals (Dahlstrom and Fuxe, 1964;Conzolazione and Cuello, 1982;Fallon and Moore, 1987). In addition, the olfactory tubercle is a limbic region of easy access and could be a relevant site of action for antidepressant drugs (Rosin et al., 1995). Citalopram was used as the selective serotonin reuptake inhibitor (SSRI) (Sitte et al., 2000). The experimental rationale was based on the assumption that incubation with low concentrations of [ 3 H]5-HT results in selective labeling of 5-HT terminals, whereas incubation of [ 3 H]5-HT in the presence of citalopram would favor labeling of catecholaminergic neurons. In addition, based on the higher affinity of the 5-HT terminals for 5-HT, we proposed that nonradioactive 5-HT should be more potent than NE and DA in displacing [3 H]5-HT, when the [ 3 H]5-HT is stored in serotonergic terminals. Such specificity should be lost if the 5-HT would be stored in catecholaminergic terminals. Our findings suggest that catecholaminergic terminals take up 5-HT when the 5-HT uptake pump is inhibited with the SSRI, citalopram.ABBREVIATIONS:5-HT, serotonin; NE, norepinephrine; DA, dopam...

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Section: Displacement Of Stored [mentioning

confidence: 99%