Effect of N1-Dansylspermine and Ro25,6981 on locomotor activity in naive mice and in the resperpinised mouse model of Parkinson's disease
Doyle, Karen M.
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Devadasan, Carol, Starr, Beryl, & Doyle, Karen M. (2016). Effect of N1-dansylspermine and Ro25,6981 on locomotor activity in naive mice and in the reserpinized mouse model of Parkinson’s disease. NeuroReport, 27(17), 1243-1247. doi: 10.1097/wnr.0000000000000685
The effect of N1-dansylspermine, a polyamine analogue and competitive polyamine antagonist, and Ro25,6981, a noncompetitive polyamine antagonist with good affinity and selectivity for the GluN2B subunit, on locomotor activity in naive mice was investigated. Furthermore, the ability of the polyamine antagonists to reverse reserpine-induced hypokinesia was assessed, 24 h after injection of a catecholamine-depleting dose of reserpine (5 mg/kg, subcutaneous), to investigate the therapeutic potential of polyamine antagonists in Parkinson’s disease. N1-dansylspermine significantly decreased locomotor activity in naive animals (P<0.001) but caused a mild, but significant increase in locomotor activity in reserpinized mice at the highest dose tested (P<0.05). Ro25,6981 significantly stimulated locomotor activity in naive animals (P<0.001) and had a slight significant stimulatory effect on reserpine-induced hypokinesia (P=0.05). N1-dansylspermine and Ro25,6981 had opposite effects on locomotor activity in naive mice, but both had a mild antiparkinsonian effect in the reserpine model. These findings suggest that antagonism of the polyamine binding site on the GluN2B subunit can reduce hypokinesia, albeit to a limited extent.