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Chronic corticosterone regulates 5-HT₁A but not 5-HT₂A agonist-induced serotonin receptor-mediated functions Lamarre, Amanda Kathleen

Abstract

There has been much research on serotonin (5-HT) 1A and 2A receptor activity, and speculation on how these receptors are implicated in the etiology of depression. Moreover, interest has been focused on mechanisms through which corticosteroids interact with these receptors to produce biochemical, physiological and behavioural changes. The 5-HT[sub 1A] and 5-HT[sub 2A] receptors appear to be controlled by corticosteroids in a biphasic manner; low corticosteroid levels exert influence on 5-HT[sub 1A] receptor activity, while high levels activate 5-HT[sub 2A] receptors. It is therefore reasonable to speculate that 5-HT[sub 1A] receptor activity predominates during normal conditions, while during times of prolonged stress, receptor activity shifts to 5-HT[sub 2A]. The purpose of this research was to investigate the hypothesis that elevated corticosterone levels cause a shift from predominantly 5-H[sub 1A] to 5-HT[sub 2A] receptor activity and that this happens over a particular time course. Corticosterone (20 mg/kg) or its vehicle was chronically administered to rats for 14 days. During this time, rats were tested at six time points on a number of 5-HT[sub 1A] and 5-HT[sub 2A] receptor-mediated physiological and behavioural measures. Overall, it was found that after 12 days of administration, rats receiving corticosterone exhibited an attenuation of the hypothermic response produced by the 5-HT[sub 1A] agonist 8-hydroxy-2(di-n-propylamino) tetralin. However, over the entire course of administration, corticosterone did not potentiate any effects produced by the 5-HT[sub 2A] receptor-agonist 1-(2,5-dimethoxy-4- iodophenyl)-2-aminopropane on 5-HT[sub 2A] receptor-mediated behaviours. These results are discussed in relation to the interaction between serotonin and HPA-axis functioning in Major Depression.

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