tailieunhanh - The therapeutic role of 5-HT2A receptor in depression and effects of escitalopram on the firing rate of 5-HT neurons in the central nervous system

Objectives: To study the therapeutic role of 5-HT2A receptor in the regulation of the serotonergic system, its functional interactions with 5-HT1A autoreceptor and effects of escitalopram (a selective serotonin (5-HT) reuptake inhibitor, SSRI) on the firing rate of 5-HT neurons in the central nervous system. | Journal of military pharmaco-medicine no7-2017 THE THERAPEUTIC ROLE OF 5-HT2A RECEPTOR IN DEPRESSION AND EFFECTS OF ESCITALOPRAM ON THE FIRING RATE OF 5-HT NEURONS IN THE CENTRAL NERVOUS SYSTEM Nguyen Thanh Hai*; Bruno P. Guiard** SUMMARY Objectives: To study the therapeutic role of 5-HT2A receptor in the regulation of the serotonergic system, its functional interactions with 5-HT1A autoreceptor and effects of escitalopram (a selective serotonin (5-HT) reuptake inhibitor, SSRI) on the firing rate of 5-HT neurons in the central nervous system. Methods: The present study was examined by using in vivo electrophysiological experiments. Results: In 5-HT2A-/- knock-out (KO) mice, a significant increase in the firing activity of dorsal raphe 5-HT neurons was observed to suggest a tonic inhibitory influence of this receptor upon serotonergic neurons. Consistent with this hypothesis, the preferential 5-HT2A receptor agonist DOI reduced the firing activity of 5-HT neurons in wild-type mice while these effects were completely blunted in 5-HT2A-/- mutants. Interestingly, in wild-type mice the lesion of the noradrenergic system attenuated the inhibitory effects of DOI on 5-HT neurons. The study showed that the inhibitory effects of the escitalopram (SSRI) currently described in wild-type mice, persisted in 5-HT1A-/- KO mice, probably in relation with hypersensitivity of 5-HT2A receptor in these mutants. Conclusion: This study clearly indicates that 5-HT2A receptor acts in concert to maintain an inhibitory influence on the serotonergic system, particularly in response of effects of the escitalopram on the increased levels of endogenous 5-HT. * Keywords: 5-HT2A receptor; 5-HT neurons; Escitalopram; Central nervous system. INTRODUCTION Selective serotonin (5-HT) reuptake inhibitors (SSRIs) are indirect-acting 5-HT receptor agonists since they block the reuptake of 5-HT, increase 5-HT extracellular concentrations in various brain regions and finally activate multiple 5-HT .