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Autoradiographic localization of 3 H‐paroxetine‐labeled serotonin uptake sites in rat brain
Author(s) -
De Souza Errol B.,
Kuyatt Brian L.
Publication year - 1987
Publication title -
synapse
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.809
H-Index - 106
eISSN - 1098-2396
pISSN - 0887-4476
DOI - 10.1002/syn.890010513
Subject(s) - dorsal raphe nucleus , serotonin , interpeduncular nucleus , olfactory tubercle , chemistry , endocrinology , raphe nuclei , medicine , paroxetine , median raphe nucleus , substantia nigra , neuroscience , biology , serotonergic , anatomy , olfactory bulb , dopamine , central nervous system , midbrain , dopaminergic , biochemistry , receptor
Paroxetine is a potent and selective inhibitor of serotonin uptake into neurons. Serotonin uptake sites have been identified, localized, and quantified in rat brain by autoradiography with 3 H‐paroxetine; 3 H‐paroxetine binding in slide‐mounted sections of rat forebrain was of high affinity (K D = 10 pM) and the inhibition affinity constant (K i ) values of various drugs in competing 3 H‐paroxetine binding significantly correlated with their reported potencies in inhibiting synaptosomal serotonin uptake. Serotonin uptake sites labeled by 3 H‐paroxetine were highly concentrated in the dorsal and median raphe nuclei, central gray, superficial layer of the superior colliculus, lateral septal nucleus, paraventricular nucleus of the thalamus, and the islands of Calleja. High concentrations of 3 H‐paroxetine binding sites were found in brainstem areas containing dopamine (substantia nigra and ventral tegmental area) and norepinephrine (locus coeruleus) cell bodies. Moderate concentrations of 3 H‐paroxetine binding sites were present in laminae I and IV of the frontal parietal cortex, primary olfactory cortex, olfactory tubercle, regions of the basal ganglia, septum, amygdala, thalamus, hypothalamus, hippocampus, and some brainstem areas including the interpeduncular, trigeminal, and parabrachial nuclei. Lower densities of 3 H‐paroxetine binding sites were found in other regions of the neocortex and very low to nonsignificant levels of binding were present in white matter tracts and in the cerebellum. Lesioning of serotonin neurons with 3,4‐methylenedioxyamphetamine caused large decreases in 3 H‐paroxetine binding. The autoradiographic distribution of 3 H‐paroxetine binding sites in rat brain corresponds extremely well to the distribution of serotonin terminals and cell bodies as well as with the pharmacological sites of action of serotonin.