Is the potent 5-HT1A receptor agonist, alnespirone (S-20499), affecting dopaminergic systems in the rat brain?

Autor: Elizabeth Mocaer, Patricia Schmitt, Bernard Renaud, Michel Hamon, C. M. Fattaccini, Christophe Dugast, Francesc Artigas, Guy Chouvet, Josep Casanovas, Monique Lesourd, Fabienne Soulière
Rok vydání: 1998
Předmět:
Male
Agonist
medicine.medical_specialty
medicine.drug_class
Dopamine
Microdialysis
5-Hydroxytryptophan
Rats
Sprague-Dawley
chemistry.chemical_compound
Neurochemical
Dopamine release
Internal medicine
medicine
Animals
Aromatic Amino Acid Decarboxylase Inhibitors
Alnespirone
Spiro Compounds
Enzyme Inhibitors
Single unit recording
Brain Chemistry
Pharmacology
Dose-Response Relationship
Drug
DOPA (3
4-dihydroxyphenylalanin)
HVA (homovanillic acid)
Dopaminergic
Brain
5-HT (5-hydroxytryptamine
serotonin) release
Receptor antagonist
Dihydroxyphenylalanine
Rats
Serotonin Receptor Agonists
Electrophysiology
Ventral tegmental area
Microdialysis in vivo
medicine.anatomical_structure
Endocrinology
chemistry
DOPAC (3
4-dihydroxyphenylacetic acid)
Receptors
Serotonin
5-HT1A receptor
Serotonin Antagonists
Alnespirone (S-20499)
5-HTP (5-hydroxytryptophan)
Extracellular Space
Receptors
Serotonin
5-HT1
medicine.drug
Zdroj: Digital.CSIC. Repositorio Institucional del CSIC
instname
ISSN: 0014-2999
DOI: 10.1016/s0014-2999(98)00254-4
Popis: The effects of the new methoxy-chroman 5-HT1A receptor agonist, alnespirone (S-20499), on the dopamine systems in the rat brain were assessed in vivo by means of electrophysiological and neurochemical techniques. Cumulative doses of alnespirone (0.032–4.1 mg kg−1, i.v.) did not modify the spontaneous firing rate of dopamine neurons in the substantia nigra as well as in the ventral tegmental area. The local application of alnespirone (0.1–10 μM) by reverse microdialysis into the dorsal striatum did not affect the dopamine output but induced a moderate, although dose-independent, increase of 5-HT (5-hydroxytryptamine, serotonin) concentrations in the dialysate. As expected of a 5-HT1A receptor agonist, intraperitoneal (i.p.) administration of alnespirone at 2–32 mg kg−1 markedly decreased 5-HT turnover in the striatum. Parallel measurements of dopamine turnover showed that alnespirone exerted no effect except at the highest dose (32 mg kg−1, i.p.) for which a significant increase was observed. Interestingly, both alnespirone-induced reduction in 5-HT turnover and increase in dopamine turnover could be prevented by pretreatment with the selective 5-HT1A receptor antagonist WAY-100635 (N-[2-[4-(2-methoxyphenyl)-1-piperazinyl]ethyl]–N-(2-pyridinyl)cyclohexane carboxamide). Altogether, these data indicate that alnespirone does not exert any direct influence on central dopamine systems. The enhanced dopamine turnover due to alnespirone at high dose appeared to result from 5-HT1A receptor stimulation, further supporting the idea that this receptor type may play a key role in 5-HT-dopamine interactions in brain.
This work was supported by INSERM, CNRS, Université Claude Bernard-Lyon-1, the Neurochemistry Department of the Instituto de Investigaciones Biomédicas de Barcelona, the Fondo de Investigacion Sanitaria (FIS 95/266) and Institut de Recherches Internationales Servier.
Databáze: OpenAIRE
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