(vi) AMI+Rotenone H&E X 20 Antioxidant and Anti-inflammatory Activities as Underlying Mechanisms of Neuroprotection by Amitriptyline in Parkinson's Disease in Rats Esraa A. Kandil, Noha F. Abdelkader, Bahia M. El-Sayeh, Samira Saleh Department of Pharmacology and Toxicology, Faculty of Pharmacy, Cairo University Introduction & Aim Effect of pretreatment with AMI on time before fall in rotarod test in rotenone-induced Parkinson’s disease in rats Effect of pretreatment with AMI on superoxide dismutase activity in rotenone-induced Parkinson’s disease in rats Previous studies suggested that early Parkinson's disease (PD) patients treated with tricyclic antidepressants experience a significant delay in the initiation of dopaminergic therapy and improvement in motor impairment and disability. Moreover, it was proposed that antidepressants might have neuroprotective properties; however, the mechanisms underlying this effect in PD are not fully understood. The current study was directed to investigate the possible role of antioxidant and anti-inflammatory activities as underlying mechanisms afforded by amitriptyline (AMI) in PD-induced in rats. Inflammatory mediators Histological Examination Effect of pretreatment with AMI on tumor necrosis factor-α level in rotenone-induced Parkinson's disease in rats Methods (i) Saline H&E X20 (ii) DMSO H&E X 20 (iii) Rotenone H&E X20 (iv) Rotenone H&E X 4 (v) AMI H&E X 20 (vi) AMI+Rotenone H&E X 20 PD was induced in adult male rats by injecting rotenone subcutaneously (s.c.) at a dose of 1.5 mg/kg every other day for a total of eleven injections. AMI was administered intraperitoneally (i.p.) at a dose of 5 mg/kg, beginning two weeks prior to rotenone injection. Adult male rats (200-270) were allocated into five groups Effect of pretreatment with AMI on inducible nitric oxide synthase expression in rotenone-induced Parkinson's disease in rats Three Normal groups Two PD groups S AMI gp. Saline gp. DMSO gp. Photomicrographs for H & E staining of midbrain sections of control, parkinsonian and AMI-treated rats (i) Normal structure (ii) Normal structure (iii) Tissue oedema (long arrow) and neuronal death (short arrow) (iv )Extensive intra ventricular hemorrhage (thick arrow) (v) Normal structure (vi) Minimal neuronal vacuolation (short arrow) and minimal perivascular oedema (long arrow) AMI + Rotenone gp. Rotenone gp. Twenty four hours after last rotenone injection and after assessment of the motor performance, rats were sacrificed. The whole brain was used for histological examination while striatal homogenate was used for determination of biochemical markers. Data are expressed as mean ± S.E.M. * Significantly different from saline group at p<0.05. # Significantly different from rotenone group at p<0.05. Oxidative stress biomarkers Results Conclusion Effect of pretreatment with AMI on malondialdehyde level in rotenone-induced Parkinson’s disease in rats Behavioral Parameters Pretreatment of parkinsonian rats with AMI improved motor performance and displayed neuronal preservation in rat brains. This was accompanied by a relief in oxidative stress parameters. Thus, there was remarkable reduction in MDA level, beside significant recovery in the activities of CAT and SOD. Furthermore, AMI administration to parkinsonian rats resulted in restraining the expression of TNF-α and iNOS. Taken together, our results suggest that anti-oxidant and anti-inflammatory activities of AMI, in the PD model in rats, could serve as important mechanisms underlying the neuroprotective effects of AMI observed clinically. Effect of pretreatment with AMI on open field test in rotenone-induced Parkinson’s disease in rats Effect of pretreatment with AMI on catalase activity in rotenone-induced Parkinson’s disease in rats