Estudo dos efeitos comportamentais e neuroquímicos da piplartina, alcamida isolada de Piper tuberculatum JACQ., em camundongos

Abstract

Piper tuberculatum Jacq. (pimenta de macaco) is a Piperaceae widely used in Northeast Brazil as a spicy or remedy. The few studies found in the literature on Piplartine (PIP), an alcamide isolated from the plant, lead us to evaluate its potential behavioral and neurobiochemical effects. The results showed that PIP (50 e 100 mg/Kg, i.p.) increased the number of grooming and rearing of mice in the open field and reversed the catalepsy induced by haloperidol. The compound also showed an anxyolitic effect, on the elevated plus maze, which was reversed by flumazenil. The hypnotic activity of PIP was registered only in the presence of ether, but not in the presence of tiopental. Despite of these effects, the drug did not induce motor coordination deficit on the animals subjected to the rota rod test. PIP (50 e 100 mg/Kg, i.p.) had an antidepressant effect, by reversing the akinesia of reserpine pre-treated animals and by decreasing the immobility time of mice subjected to the forced swimming test. In this task, the effect of PIP (20 mg/Kg, i.p.) was potentiated by imipramine (6 mg/Kg, i.p.), but not by paroxetine (1 mg/Kg, i.p.). Also, PIP (100 mg/Kg, i.p.) increased the level of NA and DA in striatum of pre-treated animals, suggesting that the drug has an antidepressant and pro-convulsant TCA-like effects. The pro-convulsant effect was noted by the decrease of the death time in PTZ-treated mice. Piplartine showed an antimuscarinic action only on the tremours induced by oxotremorine (0,5 mg/Kg, i.p.) and no other effects of the alcamide were registered on the cholinergic system of the animals treated with pilocarpine (350 mg/Kg, i.p.) or subjected to the passive-avoidance task or on the density of muscarinic (M1 + M2) receptors. PIP was devoided of antioxidant action against DPPH, but the drug decreased the concentration of TBARS and nitrite, generated on brain homogenates subjected to a thermic chock. At last, piplartine (1, 5 and 50 µg/mL) did not alter the viability of mesemcephalic rat cells and protected them from the action of 6-OHDA (10 µg/mL). The concentration of 100 µg/mL of PIP was toxic, when isolated or associated to 6-OHDA. All these findings indicate that piplartine has important effects on behavior, as the result of the interaction of the drug with some neurotransmitters systems and cellular biochemical events.