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[3H]Paroxetine Binding and Serotonin Content of Rat Cortical Areas, Hippocampus, Neostriatum, Ventral Mesencephalic Tegmentum, and Midbrain Raphe Nuclei Region Following p ‐Chlorophenylalanine and p ‐Chloroamphetamine Treatment
Author(s) -
Dewar Karen M.,
Grondin Louise,
Carli Martin,
Lima Lucimey,
Reader Tomás A.
Publication year - 1992
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.1471-4159.1992.tb09303.x
Subject(s) - dorsal raphe nucleus , serotonin , endocrinology , medicine , tegmentum , raphe nuclei , p chloroamphetamine , chemistry , midbrain , paroxetine , cingulate cortex , raphe , hippocampus , serotonergic , cerebral cortex , biology , central nervous system , receptor
Abstract: The agents p ‐chlorophenylalanine (PCPA) and p ‐chloroamphetamine (PCA) deplete brain serotonin (5‐HT) levels by two different mechanisms; PCPA inhibits the enzyme tryptophan hydroxylase, whereas PCA has a neurotoxic action on certain 5‐HT neurons. The parameters of [ 3 H]paroxetine binding to homogenates prepared from the cerebral cortex of rats treated with PCPA, PCA, or saline vehicle were investigated. The tissue concentrations of 5‐HT and 5‐hydroxyindole‐3‐acetic acid (5‐HIAA) were also determined by HPLC in the same brain samples. After PCPA treatment, neither the maximum binding capacity ( B max ) nor the dissociation constant ( K D ) of [ 3 H]paroxetine for the 5‐HT uptake recognition site differed from controls despite a substantial reduction in the concentration of 5‐HT and 5‐HIAA. In contrast, significant changes in both the B max and K D values were observed in the cerebral cortex of rats treated with PCA. Furthermore, [ 3 H]paroxetine binding and tissue concentrations of 5‐HT and 5‐HIAA were measured in the following different regions of the rat brain: cingulate, parietal, and visual cortical areas; dorsal and ventral hippocampus; rostral and caudal halves of neostriatum; ventral mesencephalic tegmentum; and midbrain raphe nuclei region after administration of PCPA, PCA, or saline vehicle. There was an excellent correlation between regional 5‐HT levels and specific [ 3 H]paroxetine binding in control and PCA‐treated rats although this correlation was lost after PCPA treatment. Under these conditions, the 5‐HT innervation remains unchanged whereas the concentration of 5‐HT and 5‐HIAA is greatly reduced. Thus, [ 3 H]paroxetine binding appears to provide a reliable marker of 5‐HT innervation density within the mammalian CNS.