Effect of the 5-HT2C Receptor Agonist WAY-163909 on Serotonin and Dopamine Metabolism across the Rat Brain: A Quantitative and Qualitative Neurochemical Study

Autor: Philippe De Deurwaerdère, Rahul Bharatiya, Abdeslam Chagraoui, Youssef Anouar, Lynn Baassiri, Julien Manem, Giuseppe Di Giovanni, Sara Whitestone
Jazyk: angličtina
Rok vydání: 2019
Předmět:
0301 basic medicine
correlative analysis
5-HT2C receptor
DOPAC
lcsh:Chemistry
chemistry.chemical_compound
0302 clinical medicine
Hydroxyindoleacetic acid
lcsh:QH301-705.5
Spectroscopy
Chemistry
Homovanillic acid
5-HIAA
Dopamine -- Metabolism
General Medicine
Computer Science Applications
serotonin
medicine.anatomical_structure
connectivity
dopamine
medicine.drug
Agonist
medicine.medical_specialty
medicine.drug_class
Infralimbic cortex
Insular cortex
Catalysis
Inorganic Chemistry
03 medical and health sciences
Neurochemical
Dopamine
Internal medicine
medicine
Physical and Theoretical Chemistry
Molecular Biology
Serotonin -- Metabolism
Organic Chemistry
3
4-Dihydroxyphenylacetic acid
HVA
030104 developmental biology
Endocrinology
lcsh:Biology (General)
lcsh:QD1-999
nervous system
Receptors
Serotonin
Orbitofrontal cortex
HPLC
metabolism
030217 neurology & neurosurgery
Zdroj: International Journal of Molecular Sciences
Volume 20
Issue 12
International Journal of Molecular Sciences, Vol 20, Iss 12, p 2925 (2019)
ISSN: 1422-0067
DOI: 10.3390/ijms20122925
Popis: The effects triggered by serotonin2C (5-hydroxytryptamin2C, 5-HT2C) receptor agonists in the brain are often subtle, and methodologies highlighting their widespread actions to account for their multiple modulatory influences on behaviors are still lacking. We report an extended analysis of a neurochemical database on monoamines obtained after the intraperitoneal administration of the preferential 5-HT2C receptor agonist WAY-163909 (0.3 and 3 mg/kg) in 29 distinct rat brain regions. We focused on the metabolite of 5-HT, 5-hydroxyindoleacetic acid (5-HIAA), the metabolites of dopamine (DA), 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA), and the index of the turnovers 5-HIAA/5-HT and DOPAC/DA. WAY-163909 increased and decreased 5-HIAA tissue levels in the amygdala and dorsolateral orbitofrontal cortex, respectively, and decreased the 5-HT turnover in the infralimbic cortex. It enhanced HVA levels in the medial orbitofrontal cortex and DOPAC levels in the amygdala. WAY-163909 increased and decreased DA turnover in the medial orbitofrontal cortex and the anterior insular cortex, respectively. The correlative analysis of the turnovers between pairs of brain regions revealed low levels of correlations across the brain but presented a distinct pattern of correlations after WAY-163909 was compared to saline-treated rats. WAY-163909, notably at 0.3 mg/kg, favored cortico-cortical and cortico-subcortical correlations of both turnovers separately, and frontal DOPAC/DA ratio with cortical and subcortical 5-HIAA/5-HT ratios at 3 mg/kg. In conclusion, the qualitative, but not the quantitative analysis shows that WAY-163909 alters the pattern of correlations across the brain, which could account for its multiple behavioral influences.
peer-reviewed
Databáze: OpenAIRE
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