BL-1023 improves behavior and neuronal survival in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-intoxicated mice

Abstract

The therapeutic potential of BL-1023, a chemical combination of L-3,4-dihydroxyphenylalanine (L-DOPA) and gamma-aminobutyric acid (GABA), was investigated in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) intoxicated mice. Such animals exhibit nigrostriatal degeneration, characteristic of human Parkinson's disease. Drug was administered during and after the development of MPTP-induced nigrostriatal lesions followed by measures of motor function and behavior, surviving nigrostriatal dopaminergic neurons and termini, and striatal dopamine levels. When administered after lesion development, BL-1023 improved motor function of MPTP-mice as measured by rotarod, total floor and vertical plane movements, and stereotypic movements in open field activity tests compared to MPTP-mice without treatment. This also paralleled modest nigral dopaminergic neuronal protection. Such significant improvements in motor function, behaviors, and dopaminergic neuronal numbers were not seen when BL-1023 was administered during MPTP-induced lesion development. The data demonstrate select abilities of BL-1023 to increase dopaminergic neuronal survival and improve motor function in MPTP-mice.