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Carleton R Sage - One of the best experts on this subject based on the ideXlab platform.

Andrew J. Grottick - One of the best experts on this subject based on the ideXlab platform.

Ben H C Westerink - One of the best experts on this subject based on the ideXlab platform.

  • augmentation of ssri effects on serotonin by 5 ht2c Antagonists mechanistic studies
    Neuropsychopharmacology, 2007
    Co-Authors: Thomas I F H Cremers, Kieran Rea, Fokko J Bosker, Hakan Wikstrom, Sandra Hogg, Arne Mork, Ben H C Westerink
    Abstract:

    The treatment of depression may be improved by using an augmentation approach involving selective serotonin reuptake inhibitors (SSRIs) in combination with compounds that focus on antagonism of inhibitory serotonin receptors. Using microdialysis coupled to HPLC, it has recently been shown that the systemic co-administration of 5-HT2C Antagonists with SSRIs augmented the acute effect of SSRIs on extracellular 5-HT. In this paper, we have investigated the mechanism through which this augmentation occurs. The increase in extracellular 5-HT was not observed when both compounds were locally infused. However, varying the route of administration for both compounds differentially revealed that an augmentation took place when the 5-HT2C antagonist was locally infused into ventral hippocampus and the SSRI given systemically, but not when systemic 5-HT2C antagonist was co-administered with the local infusion of citalopram. This suggests that the release of extracellular serotonin in ventral hippocampus may be controlled by (an)other brain area(s). As 5-HT2C receptors are not considered to be autoreceptors, this would implicate that other neurotransmitter systems are involved in this process. To investigate which neurotransmitter systems were involved in the interaction, systemic citalopram was challenged with several glutamatergic, GABA-ergic, noradrenergic, and dopaminergic compounds to determine their effects on serotonin release in ventral hippocampus. It was determined that the involvement of glutamate, norepinephrine, and dopamine in the augmentation did not seem likely, whereas evidence implicated a role for the GABA-ergic system in the augmentation.

Kevin Whelan - One of the best experts on this subject based on the ideXlab platform.

Erin K. Sanabria - One of the best experts on this subject based on the ideXlab platform.