Premium
In Vivo Labeling of Serotonin Uptake Sites with [ 3 H]Paroxetine
Author(s) -
Scheffel Ursula,
Hartig Paul R.
Publication year - 1989
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.1989.tb09215.x
Subject(s) - paroxetine , serotonin , in vivo , chemistry , neuroscience , pharmacology , biology , biochemistry , genetics , receptor
Previous work has shown that [ 3 H]paroxetine is a potent and selective in vitro label for serotonin uptake sites in the mammalian brain. In the present study, [ 3 H]paroxetine was tested in mice as an in vivo label for serotonin uptake sites. Maximum tritium concentration in the whole brain (1.4% of the intravenous dose) was reached 1 h after injection into a tail vein. Distribution of the tracer at 3 h after injection followed the distribution of serotonin uptake sites known from previous in vitro binding studies ( r = 0.85). The areas of highest [ 3 H]paroxetine concentration, in decreasing order, were: hypothalamus > frontal cortex > olfactory tubercles > thalamus > upper colliculi > brainstem > hippocampus > striatum > cerebellum. Preinjection of carrier paroxetine (1 mg/kg) significantly decreased [ 3 H]paroxetine concentration in all areas except in the cerebellum, which is known to contain a relatively low number of specific binding sites. Kinetic studies showed highest specific [ 3 H]paroxetine binding (tissue minus cerebellum) at 2 h after injection and slow clearance of activity thereafter (half‐time of dissociation from the hypothalamus, 215 min). The specificity of in vivo [ 3 H]paroxetine binding was studied by preinjecting monoamine uptake blockers or receptor antagonists 5 min before administration of [ 3 H]paroxetine. Serotonergic or muscarinic cholinergic receptor antagonists and dopamine or norepinephrine uptake blockers did not reduce the in vivo binding of [ 3 H]paroxetine. In contrast, there was an excellent correlation ( r = 0.99) between the in vivo inhibitory potencies of serotonin uptake blockers in this study and previously published in vitro data on inhibition of [ 3 H]serotonin uptake in brain synaptosomes. In addition, [ 3 H]paroxetine binding in the hypothalamus was found to be stereospecifically inhibited, (Z)‐norzimelidine displaying a greater than fourfold higher potency than the E isomer. These studies indicate that [ 3 H]paroxetine is a potent and selective agent for the in vivo labeling of cerebral serotonin uptake sites.