Prazosin addition to fluvoxamine: A preclinical study and open clinical trial in OCD.

The efficacy of selective serotonin reuptake inhibitors (SRIs) in psychiatric disorders may be "augmented" through the addition of atypical antipsychotic drugs. A synergistic increase in dopamine (DA) release in the prefrontal cortex has been suggested to underlie this augmentation effect, though the mechanism of action is not clear yet. We used in vivo microdialysis in rats to study DA release following the administration of combinations of fluvoxamine (10 mg/kg) and quetiapine (10 mg/kg) with various monoamine-related drugs.

Deep brain stimulation of the accumbens increases dopamine, serotonin, and noradrenaline in the prefrontal cortex.

Deep brain stimulation (DBS) of the nucleus accumbens (NAc) is effective in treatment-refractory obsessive-compulsive disorder and major depressive disorder. However, little is known about the neurobiological mechanisms underlying the rapid and effective changes of DBS. One of the hypotheses is that DBS modulates activity of monoamine neurotransmitters.

Unilateral deep brain stimulation in the nucleus accumbens core does not affect local monoamine release.

Recent publications have shown promising results of deep brain stimulation (DBS) in the nucleus accumbens for patients with obsessive compulsive disorder and major depressive disorder. Despite its increasing application in the clinical setting, the neurobiological mechanism of action of DBS is still uncertain. One of the possible effects of DBS might be phasic or tonic changes in monoamine release either locally in the target area or in a distant, connected region.

Synergistic dopamine increase in the rat prefrontal cortex with the combination of quetiapine and fluvoxamine.

Rationale: The combination of atypical antipsychotic drugs in addition to serotonin reuptake inhibitors has recently proven to be beneficial in a number of neuropsychiatric disorders, such as major depression, schizophrenia, and obsessive-compulsive disorder.

Objectives: To investigate the effects of an atypical antipsychotic drug in combination with a serotonin reuptake inhibitor on extracellular serotonin [5-HT]ex, and dopamine levels [DA]ex in different brain areas.

Methods: The effects of quetiapine (10 mg/kg) with fluvoxamine (10 mg/kg) on [5-HT]ex and [DA]ex were compared in the rat dorsal striatum, prefrontal cortex, nucleus accumbens (core and shell), and thalamus by means of microdialysis coupled to HPLC with electrochemical detection.

Role of extracellular serotonin levels in the effect of 5-HT1B receptor blockade.

The release of serotonin (5-HT) at serotonergic nerve terminals is regulated by 5-HT(1B) autoreceptors. Several studies have reported that the effects of selective 5-HT reuptake inhibitors (SSRIs) on extracellular 5-HT are augmented by 5-HT(1B) receptor antagonists, whereas administration of these antagonists alone do not enhance 5-HT levels. It has been suggested that 5-HT(1B) receptors have low basal endogenous activity and therefore elevated endogenous 5-HT levels are needed to elicit an effect of 5-HT(1B) receptor antagonists.