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Updated: Jul 5, 2026
Rapid In Situ Hybridization using Oligonucleotide Probes on Paraformaldehyde-prefixed Brain of Rats with Serotonin Syndrome
Published on: September 23, 2015
Cortical 5-hydroxytryptamine2A-receptor mediated excitatory synaptic currents in the rat following repeated daily
1Discovery Biology, Eli Lilly and Company, Lilly Corporate Center, Mail Drop 0510, Indianapolis, IN 46285 USA. gerard_j_marek@lilly.com
Abstract:
Down-regulation of 5-hydroxytryptamine(2A) (5-HT(2A)) receptors has been a consistent effect induced by most antidepressant drugs. The evidence for down-regulation of 5-HT(2A) receptor binding following subchronic treatment with fluoxetine and other selective serotonin reuptake inhibitors (SSRIs) is mixed. The question of 5-HT(2A) receptor sensitivity during chronic administration of antidepressants is important since activation of 5-HT(2A) receptors is associated with impulsivity. Continued activation of 5-HT(2A) receptors may functionally oppose activation of other non-5-HT(2A) receptors in the prefrontal cortex associated with the clinical efficacy of SSRI treatment. Therefore, the effects of repeated daily administration of fluoxetine (10 mg/kg, i.p. x 3 weeks) on pharmacologically characterized electrophysiological response mediated by 5-HT(2A) receptor activation, 5-HT-induced excitatory postsynaptic currents (EPSCs), in rat prefrontal cortical slices was examined. The concentration-response curve for 5-HT-induced EPSCs was unchanged following subchronic fluoxetine treatment. This subchronic fluoxetine treatment failed to modify electrophysiological responses to AMPA in layer V pyramidal cells as well. These findings would be consistent with the hypothesis that blockade of 5-HT(2A) receptors may enhance the effects of SSRIs or serotonin/norepinephrine reuptake inhibitors (SNRIs).
