Neuroprotective effect of dapsone against quinolinate- and kainate-induced striatal neurotoxicities in rats

We tested the ability of dapsone, a well-known antibiotic and antiinflammatory drug, to attenuate both the quinolinic acid (an NMDA agonist of glutamate receptors)- and kainic acid (a non-NMDA agonist of glutamate receptors)-induced in vivo neurotoxicities in rats. Circling behaviour and striatal gamma-aminobutyric acid (GABA) depletion were considered as behavioural and neurochemical end-points of brain toxicity. Rotation behaviour, evaluated six days after the intrastriatal injection of quinolinic acid (130 +/- 19 ipsilateral turns/hr), was attenuated by doses of 12.5 mg/kg and 25 mg/kg of dapsone (50 +/- 9 and 63 +/- 9 turns/hr, respectively). Striatal GABA levels (237.3 +/- 15.1 micrograms/g in control rats), found depleted at day 7 after quinolinic acid (98.3 +/- 8.6 micrograms/g), were also protected by dapsone at doses of 12.5 and 25 mg/kg (167.7 +/- 19.5 and 236.4 +/- 46.6 micrograms/g, respectively). No protective effects were observed on quinolinic acid-induced neurotoxicity, as evaluated by both parameters, at lower doses of dapsone (6.25 and 9.375 mg/kg). The action of dapsone, at the dose of 12.5 mg/kg, was also measured on kainic acid-induced depletion of the striatal GABA levels. Animals treated with dapsone + kainic acid (182.8 +/- 27.1 micrograms/g) showed significant attenuation of GABA depletion, as compared to rats treated with kainic acid alone (122.2 +/- 19.9 micrograms/g). These findings provide evidences to suggest that dapsone is acting as a neuroprotective agent against excitotoxicity induced by glutamate receptor agonists.