Serotonin 2C receptor knockout mice: Autoradiographic analysis of multiple serotonin receptors

Abstract

Quantitative receptor autoradiography was used to study possible alterations of the densities of multiple serotonin (5-HT) receptor subtypes and of serotonin transporter in the brain of 5-HT(2C) receptor knockout mice. The radioligands employed were [(3)H]citalopram, [(3)H]WAY100,635, [(3)H]8-OH-DPAT, [(3)H]GR125743, [(3)H]sumatriptan, [(3)H]MDL100,907, [(125)I](+/-)DOI, [(3)H]mesulergine, [(3)H]5-HT, [(3)H]GR113808, and [(3)H]5-CT. As expected, radioligands that label 5-HT(2C) receptors showed a complete absence of labeling in mutant mice choroid plexus and significantly reduced densities in other brain regions expressing 5-HT(2C) receptors. With the rest of the radioligands, no significant alterations in the densities of labeled sites were found in any brain region. In situ hybridization showed no changes in 5-HT(2A) receptor and serotonin transporter mRNA levels, whereas 5-HT(2C) receptor mRNA levels were reduced in certain brain regions. The present results indicate that the mouse serotonergic system does not exhibit compensatory up- or down-regulation of the majority of its components (serotonin transporter and most 5-HT receptor subtypes) in response to the absence of 5-HT(2C) receptors.

Chronic Fluoxetine Selectively Upregulates Dopamine D1-Like Receptors in the Hippocampus

“…Nonspecific binding was assessed in the presence of 1 mM of cis-flupentixol. Specific binding of serotonin 5-HT 4 receptor ligand [ 3 H]GR113808 was analyzed as described (López-Giménez et al, 2002). The brain slices were pre-incubated for 20 min in 50 mM HEPES buffer (pH 7.4, 251C) containing 10 mM pargyline and 0.01% ascorbic acid.…”

Genetic variation in cortico-amygdala serotonin function and risk for stress-related disease

“…5-HT2C-Rs are highly expressed in the mPFC and amygdala (Abramowski et al, 1995;Clemett et al, 2000;Li et al, 2003;Lopez-Gimenez et al, 2002;Molineaux et al, 1989;Pompeiano et al, 1994;Sharma et al, 1997;Wright et al, 1995). Pharmacological studies point to a role for this receptor subtype in mediating serotonin's pro-anxiety effects at the level of the amygdala.…”

The Novel Melatonin Agonist Agomelatine (S20098) Is an Antagonist at 5-Hydroxytryptamine2C Receptors, Blockade of Which Enhances the Activity of Frontocortical Dopaminergic and Adrenergic Pathways

“…Thus, 5-HT 2C receptors are enriched in the frontal cortex, hippocampus, basal ganglia, and other structures implicated in the mood, motor, and cognitive deficits that accompany depressive states (Sharma et al, 1997;Lopez-Gimenez et al, 2002). Many clinically active antidepressant agents, such as mianserin, mirtazapine, and amitriptyline, behave as antagonists at 5-HT 2C receptors (Jenck et al, 1994;Millan et al, 2000a), whereas long-term administration of 5-HT reuptake inhibitors results in their down-regulation (Bristow et al, 2000).…”