In this study, we investigated the possible antidepressant-like effect of I. paraguariensis in rats. Rats were treated for four weeks with an aqueous extract of I. paraguariensis in drinking water, following the traditional preparation of this beverage. After the period of treatment, behavioral (elevated plus-maze, open field test, and forced swimming test) and biochemical parameters (lipid peroxidation assay, thiol content, vitamin C levels, and monoamine oxidase activity) were evaluated. Animals were also analyzed on forced swimming test after 24 hours of I. paraguariensis intake. An additional group was injected with selegiline 24 hours and 30 minutes before forced swimming test as positive control. HPLC analysis revealed the profile of I. paraguariensis extract. I. paraguariensis reduced the immobility time on forced swimming test without significant changes in locomotor activity in the open field test. Any anxiolytic/anxiogenic effect of I. paraguariensis was observed in rats through the elevated plus-maze test. The antidepressant-like effect of I. paraguariensis was not accompanied by inhibitory effect on monoamine oxidase activity. There were no significant alterations on lipid peroxidation, thiol content, and vitamin C levels among the groups. In conclusion, aqueous extract of I. paraguariensis decreases the time of immobility in rats suggesting an antidepressant-like effect.

Long-term treatment with fluphenazine is associated with manifestation of extrapyramidal side effects, such as tardive dyskinesia. The molecular mechanisms related to the pathophysiology of TD remain unclear, and several hypotheses, including a role for oxidative stress, have been proposed. Harpagophytum procumbens is an herbal medicine used mainly due to anti-inflammatory effects, but it also exhibits antioxidant effects. We investigated the effect of ethyl acetate fraction of H. procumbens (EAF HP) in fluphenazine-induced orofacial dyskinesia by evaluating behavioral parameters at different times (vacuous chewing movements (VCM's) and locomotor and exploratory activity), biochemical serological analyses, and biochemical markers of oxidative stress of the liver, kidney, cortex, and striatum. Chronic administration of fluphenazine (25 mg/kg, intramuscular (i.m) significantly increased the VCMs at all analyzed times (2, 7, 14, and 21 days), and this was inhibited by EAF HP (especially at a dose of 30 mg/kg). Fluphenazine decreased locomotion and exploratory activity, and EAF HP did not improve this decrease. Fluphenazine induced oxidative damage, as identified by changes in catalase activity and ROS levels in the cortex and striatum, which was reduced by EAF HP, especially in the striatum. In the cortex, EAF HP was protective against fluphenazine-induced changes in catalase activity but not against the increase in ROS level. Furthermore, EAF HP was shown to be safe, since affected serum biochemical parameters or parameters of oxidative stress in the liver and kidney. These findings suggest that the H. procumbens is a promising therapeutic agent for the treatment of involuntary oral movements.

Typical antipsychotics, which are commonly used to treat schizophrenia, cause motor disorders such as tardive dyskinesia (TD) in humans and orofacial dyskinesia (OD) in rodents. The disease mechanisms as well as treatment effectiveness are still unknown. In this study, we investigated the effect of resveratrol, a polyphenol with neuroprotective properties, on behavioral changes induced by chronic treatment with fluphenazine in rats and the possible relationship between monoamine oxidase (MAO) activity and vacuous chewing movements (VCMs). Rats were treated for 18 weeks with fluphenazine enantate [25 mg/kg, intramuscularly (i.m.), every 21 days] and/or resveratrol (20 mg/kg, offered daily in drinking water). Next, body weight gain, behavioral parameters (VCMs and open field tests-locomotor and rearing activity), and MAO activity were evaluated. Fluphenazine treatment reduced body weight gain, number of crossings and rearings, and the co-treatment with resveratrol did not affect these alterations. Fluphenazine increased the prevalence and intensity of VCMs and the co-treatment with resveratrol reduced the VCMs. Furthermore, a negative correlation was found between the number of VCMs and MAO-B activity in the striatum of rats. Our data suggest that resveratrol could be promissory to decrease OD. Moreover, MAO-B activity in the striatum seems to be related to VCMs intensity.

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