Group III mGlu receptor agonists produce anxiolytic- and antidepressant-like effects after central administration in rats.
Neuropharmacology
; 46(2): 151-9, 2004 Feb.
Article
en En
| MEDLINE
| ID: mdl-14680755
It was well established that compounds which decrease glutamatergic transmission via blockade of NMDA or group I mGlu receptors produce anxiolytic- and antidepressant-like action in animal tests and models. Since group III metabotropic glutamate receptor (mGluR) agonists are known to reduce glutamatergic neurotransmission by the inhibition of glutamate release, we decided to investigate potential anxiolytic- and/or antidepressant-like effects of group III mGluR agonists, after central administration in rats. It was found that group III mGluR agonists, (1S,3R,4S)-1-aminocyclo-pentane-1,3,4-tricarboxylic acid (ACPT-I) and 2-amino-4-(3-hydroxy-5-methylisoxazol-4-yl)butyric acid (HomoAMPA), given intrahippocampally, produced a dose-dependent anxiolytic-like effect in the conflict drinking test. The effects of ACPT-I and HomoAMPA were reversed by (RS)-alpha-cyclopropyl-4-phosphonophenyl glycine (CPPG), group III mGluR antagonist. Moreover, a dose-dependent antidepressant-like action of group III mGluR agonists, ACPT-I and (RS)-4-phosphonophenylglycine (RS-PPG), but not HomoAMPA, was found in behavioral despair test, after intracerebroventricular injections, and the effect of ACPT-I was reversed by CPPG. The results obtained indicate that group III mGluR agonists produce anxiolytic- as well as antidepressant-like effects in behavioral tests, after central administration in rats. The reduction of glutamate release by group III mGluR activation may be a possible mechanism underlying anxiolytic- and antidepressant-like properties of the tested compounds. In conclusion, the results of our studies indicate that group III mGlu receptor agonists may play a role in the therapy of both anxiety and depression.
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Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Ansiolíticos
/
Receptores de Glutamato Metabotrópico
/
Ácido alfa-Amino-3-hidroxi-5-metil-4-isoxazol Propiónico
/
Hipocampo
/
Antidepresivos
Límite:
Animals
Idioma:
En
Revista:
Neuropharmacology
Año:
2004
Tipo del documento:
Article
País de afiliación:
Polonia
Pais de publicación:
Reino Unido