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The selective serotonin reuptake inhibitors (SSRIs) are the most frequently prescribed antidepressant drugs, because they are well tolerated and have no severe side effects. They rapidly block serotonin (5-HT) reuptake, yet the onset of their therapeutic action requires weeks of treatment. This delay is the result of presynaptic and postsynaptic adaptive(More)
The antidepressant drug clomipramine (CIM) blocks 5-hydroxytryptamine (5-HT) uptake in vitro. Electrophysiological studies have shown that CIM also reduces the firing of serotonergic neurons in the dorsal raphe nucleus. In order to assess the effects of CIM on serotonergic transmission in vivo, the technique of intracerebral microdialysis was used. CIM was(More)
The prefrontal cortex plays a key role in the control of higher brain functions and is involved in the pathophysiology and treatment of schizophrenia. Here we report that approximately 60% of the neurons in rat and mouse prefrontal cortex express 5-HT(1A) and/or 5-HT2A receptor mRNAs, which are highly co-localized (approximately 80%). The electrical(More)
The release of dopamine in the ventral tegmental area (VTA) plays an important role in the autoinhibition of the dopamine neurons of the mesocorticolimbic system through the activation of somatodendritic dopamine D2 autoreceptors. Accordingly, the intra-VTA application of dopamine D2 receptor agonists reduces the firing rate and release of dopamine in the(More)
Since 1994, the beta-adrenoceptor and 5-HT(1A/1B) receptor ligand pindolol has been used to accelerate or enhance the clinical effects of antidepressant drugs, such as the selective 5-HT reuptake inhibitors (SSRIs), that act primarily on 5-HT-containing neurones. Pindolol was initially thought to act by preventing the inhibition of 5-HT release, elicited by(More)
1. Using brain microdialysis, we compared the relative role of 5-hydroxytryptamine (5-HT; serotonin) blockade and somatodendritic 5-HT(1A) and/or terminal 5-HT(1B) autoreceptor activation in the control of 5-HT output. 2. Fluoxetine (10 mg kg(-1) i.p.) doubled the 5-HT output in frontal cortex and dorsal hippocampus. The 5-HT(1A) receptor antagonist WAY(More)
In the rat, postsynaptic 5-hydroxytryptamine2A receptors medial prefrontal cortex control the activity of the serotonergic system through changes in the activity of pyramidal neurons projecting to the dorsal raphe nucleus. Here we extend these observations to mouse brain. The prefrontal cortex expresses abundant 5- hydroxytryptamine2A receptors, as assessed(More)
Existing antidepressant treatments exhibit limited efficacy and a slow onset of action. Several neurobiological adaptive mechanisms might delay the clinical effects of antidepressants, whose therapeutic action is primarily triggered by an increase of serotonergic and noradrenergic neurotransmission. Here, we review several potential mechanisms that could be(More)
Several genetic, neurodevelopmental, and pharmacological animal models of schizophrenia have been established. This short review examines the validity of one of the most used pharmacological model of the illness, ie, the acute administration of N-methyl-D-aspartate (NMDA) receptor antagonists in rodents. In some cases, data on chronic or prenatal NMDA(More)
The release of 5-HT in terminal areas of the rodent brain is regulated by 5-HT1B receptors. Here we examined the role of 5-HT1B receptors in the control of 5-HT output and firing in the dorsal raphe nucleus (DR), median raphe nucleus (MnR) and forebrain of the rat in vivo. The local perfusion (30-300 microM) of the selective 5-HT1B receptor agonist(More)