Strain-dependent serotonin neuron feedback control: role of serotonin2C receptors
- Resource Type
- Authors
- Roberto W. Invernizzi; Eleonora Calcagno
- Source
- Journal of Neurochemistry. 114:1701-1710
- Subject
- Agonist
medicine.medical_specialty
medicine.drug_class
Citalopram
Biology
Receptor antagonist
Biochemistry
Cellular and Molecular Neuroscience
chemistry.chemical_compound
Endocrinology
Dorsal raphe nucleus
chemistry
Internal medicine
medicine
Serotonin 5-HT2 Receptor Antagonists
Serotonin
Neurotransmitter
Behavioural despair test
medicine.drug
- Language
- ISSN
- 0022-3042
We investigated the role of serotonin(2C) receptor-mediated feedback mechanisms in the response to citalopram in C57BL/6 and DBA/2 mice, which are respectively responders and non-responders to selective serotonin reuptake inhibitors in the forced swimming test. The microdialysis technique was used to assess changes in extracellular serotonin and GABA in the mouse dorsal raphe (DR). Citalopram (1.25-20 mg/kg) raised extracellular serotonin and GABA in the DR of both mouse strains. These effects were abolished by depleting brain serotonin with p-chlorophenylalanine (300 mg/kg × 3). Systemic and/or intra-DR infusion of the serotonin(2C) receptor antagonist 6-chloro-5-methyl-1-[[2-[(2-methyl-3-pyridyl)oxy]-5-pyridyl]carbamoyl]-indoline (1 mg/kg and 0.1 μM, respectively) enhanced citalopram's effect on extracellular serotonin in the DR and medial prefrontal cortex and abolished the rise of GABA in the DR of DBA/2 mice but had no effect in C57BL/6 mice. The serotonin(2C) receptor agonist Ro60-0175 (0.03-3.0 mg/kg) reduced extracellular serotonin and raised GABA in the DR of DBA/2 mice but had much less effect in C57BL/6 mice. These findings show that the sensitivity of serotonin(2C) receptors determines the efficacy of augmentation strategies aimed at enhancing the effect of serotonin reuptake inhibitors on extracellular serotonin through the suppression of serotonin(2C) receptor-mediated feedback control of serotonin neurons.