Inhibitors of GABA metabolism: Implications for Huntington's disease

Abstract

Stereotaxic injection of kainic acid into rat striatum produces neuronal degeneration and neurochemical alterations resembling Huntington's disease (HD). Since correction of the deficiency in γ‐aminobutyric acid (GABA) in HD may be of therapeutic value, the efficacy of drugs that inhibit the GABA‐degrading enzyme (GABA‐T) in elevating the levels of GABA has been examined in the animal model for HD. High doses of di‐N‐propylacetic acid only partially correct the GABA deficiency in the striatum, whereas low doses of γ‐acetylenic GABA, a specific irreversible inhibitor of GABA‐T, completely restore the levels of GABA in striatum and substantia nigra.