Antidepressant-like effect of the mGluR5 antagonist MTEP in an astroglial degeneration model of depression
PBN-AR
Instytucja
Instytut Farmakologii im. Jerzego Maja Polskiej Akademii Nauk
Informacje podstawowe
Główny język publikacji
en
Czasopismo
BEHAVIOURAL BRAIN RESEARCH
ISSN
0166-4328
EISSN
1872-7549
Wydawca
ELSEVIER SCIENCE BV
DOI
URL
Rok publikacji
2014
Numer zeszytu
Strony od-do
23-33
Numer tomu
273
Identyfikator DOI
Liczba arkuszy
Słowa kluczowe
en
Gliotoxin;
L-AAA;
Depression;
mGluR5 antagonist;
MTEP
Streszczenia
Język
en
Treść
The glutamatergic predominance in the excitatory-inhibitory balance is postulated to be involved in the pathogenesis of depression. Such imbalance may be induced by astrocyte ablation which reduces glutamate uptake and increases glutamate level in the synaptic cleft. In the present study, we tried to ascertain whether astroglial degeneration in the prefrontal cortex could serve as an animal model of depression and whether inhibition of glutamatergic transmission by the mGluR5 antagonist MTEP could have antidepressant potential. Astrocytic toxins L-or PL-alpha-aminoadipic acid (AAA), 100 mu g/2 mu l, were microinjected, bilaterally into the rat medial prefrontal cortex (PFC) on the first and second day of experiment. MTEP (10 mg/kg) or imipramine (30 mg/kg) were administered on the fifth day. Following administration of MTEP or imipramine the forced swim test (FST) was performed for assessment of depressive-like behavior. The brains were taken out for analysis on day eight. The astrocytic marker, glial fibrillary acidic protein (GFAP) was quantified in PFC by Western blot method and by stereological counting of immunohistochemically stained sections. Both L-AAA and DL-AAA induced a significant increase in immobility time in the FST. This effect was reversed by imipramine, which indicates depressive-like effects of these toxins. A significant decrease in GFAP (about 50%) was found after L-AAA. Both the behavioral and GFAP level changes were prevented by MTEP injection. The obtained results indicate that the degeneration of astrocytes in the PFC by L-AAA may be a useful animal model of depression and suggest antidepressant potential of MTEP.
Cechy publikacji
ORIGINAL_ARTICLE
Inne
System-identifier
PX-56989cd3810641ecf9198e18
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