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Electrophysiological studies on the effects of antidepressant drugs and corticosterone on serotonin receptors in the hippocampus

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Disturbances in the serotonin (5-HT) system and the limbic-hypothalamo-pituitary-adrenal axis (LHPA) have been implicated in the pathophysiology of depression. It is well established that hippocampus is a central component of limbic circuitry that participates in the modulation of cognition, mood and behavior, and is involved in the control of the LHPA axis. Therefore, the hippocampus provides a unique environment to study the interplay between serotonergic system, antidepressants and corticosteroids. Activity of hippocampal cells can be modulated by 5-HT via inhibitory 5-HT1A and excitatory 5-HT4 receptors. Repeated treatment with antidepressants increases the responsiveness of hippocampal pyramidal neurons to the 5-HT1A and attenuates the responsiveness to the 5-HT4 receptor agonists, with a time course which correlates with the delayed onsed of the therapeutic effect of antidepressants in humans. Moreover, repeated corticosterone, which may constitute a model of a prolonged nonadaptable stress, has opposite effect on hippocampal responsiveness to the 5-HT1A and 5-HT4 receptor activation. Such an action results in an enhancement of the 5-HT-mediated inhibition by antidepressants and a reduction in the inhibitory effect of 5-HT by corticosterone which may be relevant to antidepressant/antiaxiety and proaxiety effects, respectively, of both treatments.




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A. Zahorodna, Instytut Farmakologii PAN, ul. Smetna 12, 31-343 Krakow, Poland


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