Neuroprotective effect of lamotrigine and MK-801 on rat brain lesions induced by 3-nitropropionic acid: Evaluation by magnetic resonance imaging and in vivo proton magnetic resonance spectroscopy

Magnetic resonance imaging and in vivo proton magnetic resonance spectrosco py were used to evaluate the therapeutic effect of lamotrigine and MK-801 o n rat brain lesions induced by 3-nitropropionic acid. Systemic administrati on of 3-nitropropionic acid (15 mg/kg per day) to two-month-old Sprague-Daw ley rats (n = 10 for each group) for five consecutive days induced selectiv e striatal and hippocampal lesions and specific behavioral change. Pretreat ment with lamotrigine(10 mg/kg or 20 mg/kg per day) or MK-801 (2 mg/kg per day) attenuated the lesions and behavioral change. There were no significan t differences in T2 values of the striatum and hippocampus among rats pretr eated with MK-801, lamotrigine (20 mg/kg) and sham controls. Significant el evations of succinate/creatine and lactate/creatine ratios and decreases of N-acetylaspartate/creatine and choline/creatine ratios were observed after 3-nitropropionic acid injections (P < 0.001). The changes were nearly prev ented after pretreatment with lamotrigine (20 mg/kg). However, the N-acetyl aspartate/creatine in rats pretreated with lamotrigine (10 mg/kg) (P < 0.01 ) and MK-801 (P < 0.05) still showed significant reduction as compared with sham controls. Thus we conclude that both lamotrigine and MK-801 are effective in attenuat ion of brain lesions induced by 3-nitropropionic acid. A higher dose of lam otrigine provides a better neuroprotective effect than MK-801. With a bette r therapeutic effect and fewer side effects, lamotrigine is more promising for potential clinical application. (C) 1999 IBRO. Published by Elsevier Sc ience Ltd.