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Electrophysiological studies on adaptive changes of serotonin receptors using spontaneous epileptiform activity in neuronal network

100%
Bobula B., Zahorodna A., Tokarski K., Hess G.
Postępy Higieny i Medycyny Doświadczalnej
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2002
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vol. 56
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issue 3
377-383
EN
Certain antidepressant medications exert effects on the serotonergic (5-HT) syste but their machanisms are still not well understood. Using extracellular ex vivo recording of spontaneous, epileptiform activity of neurons we determined changes in the reactivity of cortical and hippocampal slices to agonists of main subtypes 5-HT receptors, induced by repeated administration of the antidepressants . Repeated treatment with antidepressants enhances the 5-HT-mediated inhibition in both frontal cortex and hippocampal regions. Drugs administration induce opposite adaptive changes within 5-HT2 and 5-HT1A receptors in frontal cortex as well as in 5-HT1A and 5-HT4 receptors in the hippocampus. These effects may contribute to therapeutic effects of antidepressants administration.
2

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

100%
Zahorodna A., Tokarski K., Bijak M.
Postępy Higieny i Medycyny Doświadczalnej
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2000
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vol. 54
|
issue 3
391-401
EN
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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