Effect of p-chloroamphetamine on 5-HT1A and 5-HT7 serotonin receptor expression in rat brain

The aim of this study was to investigate if p-chloroamphetamine (PCA), whic h is neurotoxic to serotonin (5-HT) nerve terminals, was able to induce, li ke 3,4-methylenedioxymethamphetamine, a region-specific regulation of 5-HT1 A receptor mRNA expression. The effect of PCA on the expression of 5-HT7 re ceptors, which share some pharmacological properties with 5-HT1A receptors, was comparatively studied. PCA (2 x 5 mg/kg) produced a lasting depletion of 5-HT content in the rat frontal cortex and hippocampus. In the hippocamp us, the maximal 5-HT depletion was found on day 21 (-70%), whereas in the c ortex, the highest 5-HT depletion was found on day 14 (-73%), with a partia l but significant recovery on day 21. At the latter time point, 5-HT1A rece ptor mRNA expression was increased by 80% in the cortex and decreased by 50 % in the hippocampus. The 5-HT1A receptor mRNA expression was also enhanced after exposure to PCA of rat cortical but not of hippocampal primary cultu res. In regard to 5-HT7 receptor mRNA expression, the most remarkable chang e after PCA was the great increase (+200%) in the brainstem. Binding studie s to 5-HT1A receptors matched the changes in receptor mRNA expression. Gel shift assays revealed enhanced nuclear protein binding to the kappa B seque nce with use of cortical but not hippocampal extracts of PCA-treated rats. Overall, the data show region-specific changes in 5-HT receptor-type expres sion that may not be entirely dependent on the neurotoxic effect of PCA on 5-HT terminals.