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BACKGROUND AND PURPOSE Smoking cessation trials with three high-affinity partial agonists of alpha4beta2 neuronal nicotinic acetylcholine receptors (nAChRs) have demonstrated differences in their clinical efficacy. This work examines the origin of the differences by taking into account brain exposure and pharmacological effects at human alpha4beta2 nAChRs.(More)
BACKGROUND We investigated the combination of selective serotonin reuptake inhibitors (SSRIs) with the beta-adrenoceptor/serotonin 1A (5-HT(1A)) antagonist pindolol, based on the concept that 5-HT(1A) receptor blockade would eliminate the need for desensitization of presynaptic 5-HT(1A) receptors and therefore hasten the onset of action and improve the(More)
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-HT(2C) antagonists with(More)
[18F]MPPF is a selective serotonin-1A (5-HT1A) receptor antagonist and may be used to measure changes in the functional levels of serotonin (5-HT). The technique is based on the assumption that the injected radiolabeled ligand competes for the same receptor as the endogenous transmitter. Results from studies using serotonergic ligands are not always(More)
We have investigated effects of continuous SSRI administration and abrupt discontinuation on biochemical and behavioral indices of rat brain serotonin function, and attempted to identify underlying mechanisms. Biochemistry of serotonin was assessed with brain tissue assays and microdialysis; behavior was assessed as the acoustic startle reflex. Long-term(More)
GABA and glutamate sampled from the brain by microdialysis do not always fulfill the classic criteria for exocytotic release. In this regard the origin (neuronal vs. astroglial, synaptic vs. extrasynaptic) of glutamate and GABA collected by microdialysis as well as in the ECF itself, is still a matter of debate. In this overview microdialysis of GABA and(More)
The enhancement of central serotonin system function underlies the therapeutic effects of selective serotonin reuptake inhibitors (SSRIs), which have become the most commonly used class of antidepressant agents. However, many individuals experience depressive episodes that are resistant to SSRI treatment. Homeostatic mechanisms that limit the extent to(More)
RATIONALE Male wild house-mice genetically selected for long attack latency (LAL) and short attack latency (SAL) differ in structural and functional properties of postsynaptic serotonergic-1A (5-HT(1A)) receptors. These mouse lines also show divergent behavioral responses in the forced swimming test (FST, i.e., higher immobility by LAL versus SAL mice). (More)
RATIONALE Serotonin (5-HT)(2C) receptors are implicated in the control of mood, and their blockade is of potential interest for the management of anxiodepressive states. OBJECTIVES Herein, we characterized the in vitro and in vivo pharmacological profile of the novel benzourea derivative, S32006. MATERIALS AND METHODS Standard cellular,(More)
Selective serotonin reuptake inhibitors are the most widely prescribed antidepressant drugs. However, they exhibit a slow onset of action, putatively due to the initial decrease in serotonin cell firing mediated via somato-dendritic autoreceptors. Interestingly, blockade of 5-HT(2C) receptors significantly potentiates the effect of citalopram, a selective(More)