FURTHER INVESTIGATIONS ON BRAIN DISTRIBUTION OF HYDRA ZINE AND ITS γ-AMINOBUTYRIC ACID ELEVATING EFFECT IN RATS

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Perry's hypothesis that hydrazine (Hz) derived from isoniazid (INH) treatment plays an important role in the elevation of brain γ-aminobutyric acid (GABA) levels¹⁾ was reexamined by measuring Hz and GABA levels in the brain after the treatment with 50 mg/kg of INH or different doses of Hz. The treatment with 50 mg/kg of INH to rats resulted in the elevation of GABA levels in rat whole brain. The maximum levels of GABA increased about twice at 4h from 2.06±0.4μmol/g wet wt. in the control group to 3.61±0.4μmol/g wet wt. in INH treated group. In this case, brain levels of Hz ranged from 25.6 to 80.8 ng/g wet wt. within 10 h. On the other hand, Hz levels after the treatment with 0.5 mg/kg of Hz were about five times higher than those after INH treatment. However, 0.5mg/kg of Hz treatment did not increase brain GABA levels at all. Perry's hypothesis was denied by the fact that brain Hz levels after INH treatment were too low to elevate brain GABA levels.