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Effect of p ‐Chloroamphetamine on 5‐HT 1A and 5‐HT 7 Serotonin Receptor Expression in Rat Brain
Author(s) -
GarcíaOsta Ana,
Frechilla Diana,
Del Río Joaquín
Publication year - 2000
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 - 10.1046/j.1471-4159.2000.0741790.x
Subject(s) - p chloroamphetamine , receptor , serotonin , 5 ht receptor , hippocampus , 5 ht1a receptor , medicine , endocrinology , hippocampal formation , receptor expression , biology , cortex (anatomy) , chemistry , serotonergic , neuroscience
The aim of this study was to investigate if p ‐chloroamphetamine (PCA), which is neurotoxic to serotonin (5‐HT) nerve terminals, was able to induce, like 3,4‐methylenedioxymethamphetamine, a region‐specific regulation of 5‐HT 1A receptor mRNA expression. The effect of PCA on the expression of 5‐HT 7 receptors, which share some pharmacological properties with 5‐HT 1A receptors, was comparatively studied. PCA (2 × 5 mg/kg) produced a lasting depletion of 5‐HT content in the rat frontal cortex and hippocampus. In the hippocampus, the maximal 5‐HT depletion was found on day 21 (‐70%), whereas in the cortex, the highest 5‐HT depletion was found on day 14 (‐73%), with a partial but significant recovery on day 21. At the latter time point, 5‐HT 1A receptor mRNA expression was increased by 80% in the cortex and decreased by 50% in the hippocampus. The 5‐HT 1A receptor mRNA expression was also enhanced after exposure to PCA of rat cortical but not of hippocampal primary cultures. In regard to 5‐HT 7 receptor mRNA expression, the most remarkable change after PCA was the great increase (+200%) in the brainstem. Binding studies to 5‐HT 1A receptors matched the changes in receptor mRNA expression. Gel shift assays revealed enhanced nuclear protein binding to the κB sequence with use of cortical but not hippocampal extracts of PCA‐treated rats. Overall, the data show region‐specific changes in 5‐HT receptor‐type expression that may not be entirely dependent on the neurotoxic effect of PCA on 5‐HT terminals.