[Interstrain differences in the content of excitatory and inhibitory amino acids in the brain of DBA/2J, Balb/c and C57BL/6 mice: characteristics of the effect of a dipeptide antipsychotic drug dilept].
We have performed a comparative study of the content of glutamate (Glu), aspartate (Asp), taurine (Tau), glycine (Gly) and gamma-amino-butyric acid (GABA) in the cortex, hippocampus, and striatum of the DBA/2J, Balb/c and C57BL/6 mice brain. The levels of Glu, Tau and GABA in DBA/2J hippocampus was lower than those in other experimental strains. These findings are consistent with published data on the specific neurophysiological properties of DBA/2J (neuroleptic sensitive prepulse inhibition, deficit), thus allowing this strain to be used in modeling schizophrenia. Taking into account these facts, in the next step we investigated the effects of dilept, the new neurotensine-derived dipeptide with antipsychotic activity (GZR-123, methyl ester of N-caproyl-L-prolyltyrosine), on the content of neurotransmitter acids in DBA/2J mice brain structures. In a dose of 0.8 mg/kg (i.p.) dilept induced a statistically significant increase in the levels of Glu, Tau and GABA in striatum of DBA/2J, as well as insignificant increase in the levels of these amino acids in the cortex. These effects are quite similar to those described for the parent peptide neurotensine, in case of its intracerebral administration. The results of our study prove the necessity of the further development of dilept as a potential antipsychotic drug.
Shubenina
E B
EB
Kudrin
V S
VS
Klodt
P M
PM
Pokrovskiĭ
A A
AA
Gudasheva
T A
TA
Voronina
T A
TA
Ostrovskaia
R U
RU
D000596:Amino Acids / Q000378:metabolism*; D000818:Animals; D014150:Antipsychotic Agents / Q000494:pharmacology*; D001921:Brain / Q000187:drug effects / Q000378:metabolism*; D018846:Excitatory Amino Acids / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D011392:Proline / Q000031:analogs & derivatives* / Q000494:pharmacology; D013045:Species Specificity; D014443:Tyrosine / Q000031:analogs & derivatives* / Q000494:pharmacology
D000596:Amino Acids; D014150:Antipsychotic Agents; D018846:Excitatory Amino Acids; C401484:GZR 123; D014443:Tyrosine; D011392:Proline