THE EFFECTS OF L-DEPRENYL TREATMENT, ALONE AND COMBINED WITH GM1 GANGLIOSIDE, ON STRIATAL DOPAMINE CONTENT AND SUBSTANTIA-NIGRA PARS COMPACTA NEURONS

The present study examined the effects of GM1 ganglioside and the mono amine oxidase B (MAO-B) inhibitor L-deprenyl, alone and in combination , on striatal dopamine (DA) and DOPAC levels, and the density of tyros ine hydroxylase (TH) positive neurons in the substantia nigra pars com pacta (Nc) of C57b1/6J mice following MPTP administration (20 mg/kg, s .c., twice daily for 5 days). GM1 treatment (30 mg/kg, i.p., daily for 3 weeks, beginning 24 h after the last MPTP injection) partially rest ored striatal DA levels and rescued SNc neurons. A high dose of L-depr enyl, inhibiting MAO-B activity, (10 mg/kg, i.p. every other day for 3 weeks beginning 3 days after the last MPTP injection) increased stria tal DA content, but did not rescue TH-positive SNc neurons. A low dose of L-deprenyl (0.01 mg/kg, i.p. every other day for 3 weeks beginning 3 days after the last MPTP injection) had no effect on either striata l neurochemistry or the rescue of SNc TH-positive neurons. Co-administ ration of GM1 and high dose L-deprenyl caused a synergistic increase i n striatal DA levels, above that obtained with either GM1 or high dose L-deprenyl alone. Co-administration of GM1 and low dose L-deprenyl wa s not only not synergistic, but caused GM1s effects to be antagonized. The results do not confirm previous findings that low dose L-deprenyl administration in vivo after MPTP can rescue SNc neurons. Given GM1's potential as an adjunct to present anti-parkinsonian medications whic h include L-deprenyl, it will be important to further investigate the interactions between these two potential therapies. (C) 1998 Elsevier Science B.V.