Long-lasting antidepressant-like activity of the GPR39 zinc receptor agonist TC-G 1008.
J Affect Disord
; 245: 325-334, 2019 02 15.
Article
en En
| MEDLINE
| ID: mdl-30419533
ABSTRACT
BACKGROUND:
The discovery of the zinc-sensing receptor, has provided new possibilities for explaining the neurobiology of zinc. Recent studies indicate that the GPR39 zinc receptor may play an important role in the pathogenesis of depression as well as in the antidepressant mechanism of action.METHODS:
In this study we evaluated the time-course of the antidepressant response of the GPR39 agonist (TC-G 1008), imipramine, ZnCl2 and MK-801 in the forced swim test in mice 30â¯min, 3â¯h, 6â¯h and 24â¯h after acute drug administration as well as after 14-day treatment. Zinc level was measured in serum of mice. BDNF protein level was evaluated in hippocampus following both acute and chronic TC-G 1008 treatment.RESULTS:
A single administration of the GPR39 agonist caused an antidepressant-like effect lasting up to 24â¯h following the injection, which is longer than the effect of imipramine, ZnCl2 and MK-801. Chronic treatment with these compounds caused a decrease in immobility time in the FST. Serum zinc concentrations showed an increased level following chronic ZnCl2 administration, but not following administration of TC-G 1008, imipramine or MK-801. We also observed some tendencies for increased BDNF following acute TC-G 1008 treatment.LIMITATIONS:
TC-G 1008 is new drug designed to study GPR39 therefore additional pharmacodynamic and pharmacokinetic properties in preclinical studies are required.CONCLUSION:
This study shows for the first time the long-lasting antidepressant effect of the GPR39 agonist in comparison with imipramine, ZnCl2 and MK-801. Our findings suggest that GPR39 should be considered as a target in efforts to develop new antidepressant drugs.Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Pirimidinas
/
Sulfonamidas
/
Receptores Acoplados a Proteínas G
/
Depresión
/
Antidepresivos
Límite:
Animals
Idioma:
En
Revista:
J Affect Disord
Año:
2019
Tipo del documento:
Article
País de afiliación:
Polonia
Pais de publicación:
HOLANDA
/
HOLLAND
/
NETHERLANDS
/
NL
/
PAISES BAJOS
/
THE NETHERLANDS