Figure 1.

HCT1026 inhibits MPTP-induced loss of high affinity synaptosomial [³H]DA uptake and reverses motor impairment. Young and ageing C57Bl/6 mice fed with a control, flurbiprofen or HCT1026 diets (30 mg kg^-1) starting at -10 d, underwent an MPTP treatment according to the subacute (A) or subchronic (B), injection paradigms, as described. Age-matched mice fed with the different diets received physiologic saline (NaCl, 10 ml kg^-1) and served as controls. Seven days after MPTP discontinuance, loss of DAergic functionality was assessed in striatum measuring high affinity synaptosomial striatal [³DA] uptake [8]. HCT1026 prooved to be more potent than its parent compound in counteracting MPTP-induced decreases in striatal DA uptake levels in both the subacute (A) and subchronic (B) protocols. Differences were analyzed by ANOVA followed by Newman-Keuls test, and considered significant when p < 0.05. **p < 0.05 vs saline, ° p < 0.05 vs MPTP + control diet. C. Ageing mice fed with a control or HCT1026 diets, were submitted to the subchronic MPTP regimen, and striatal DA uptake levels measured 21, 30 and 40 d after MPTP (n = 6/time point). Note the long-lasting counteraction of MPTP-induced striatal toxicity in mice fed with HCT1026 as opposed to the control diet. D: Motor performances on Rotarod of saline- and MPTP-treated mice (n = 10/group) fed with a control or HCT1026 diets. Time of permanence on revolving bars (ordinate) are plotted against pre- and post-treatment days (5 trials/day) during which experiments were performed. Mean and SEM values are reported. Establishment of a motor deficit measured 1-7 dpt, is counteracted by HCT1026. Differences were analyzed as above. ** p < 0.05 vs saline; ° p < 0.05 vs MPTP + control diet.