Effect of amitriptyline on learning and memory consolidation in the male Wistar rats with an experimental model of pentylenetetrazole-induced seizure

Abstract Amitriptyline (AMT) was developed for the treatment of chronic and neuropathic pain. There is also evidence it may be useful in the treatment of neurodegenerative disorders. In this regard, the effect of on the experimental model of seizures and memory impairment caused by seizures in rats is investigated in the present study. Seizures in Wistar rats (200-250 g) were induced by pentylenetetrazole (PTZ, 60 mg/kg, intraperitoneally (i.p.)). The anticonvulsant effect of AMT (10 and 20 mg/kg, i.p.) was evaluated in the seizure model. The effect on memory was assessed using passive avoidance (PA) learning and memory test. After behavioral tests, the animals underwent deep anesthesia and were put down painlessly. Animal serum was isolated for oxidant/antioxidant assays (malondialdehyde (MDA), and glutathione peroxidase (GPx)). Intraperitoneal injection of AMT decreased the mean number of myoclonic jerks and generalized tonic-clonic seizure (GTCS) duration and increased the mean latency of myoclonic jerk and GTCS compared to the PTZ group. Moreover, in the PA test, AMT caused a significant increase in retention latency (RL) and total time spent in the light compartment (TLC) compared to the PTZ group. Biochemical tests showed that AMT was able to significantly increase GPx serum levels and significantly reduce MDA serum levels compared to the PTZ group. Overall, this study suggests the potential neuroprotective effects of the AMT drug in a model of memory impairment caused by seizures via the mechanism of inhibition of the oxidative stress pathway.

Antinociceptive activity of Ricinus communis seed's hydroethanolic extract on male Balb/C mice / Atividade antinociceptiva do extrato hidroetanolico de sementes de Ricinus communis em ratos machos

ABSTRACT: Pain is a normal protective response to tissue injury caused by physical trauma, noxious chemicals and microbiological agents. Use of chemical drugs and medicinal plants is a conventional method to manage pain; however, their side effects have caused increased tendency to the use of herbal medicines among patients. This study was conducted to investigate antinociceptive action of Ricinus communis seed's extract (RCE) in male Balb/C mice. In this experimental study, 72 male mice weighing 25-35gr were used. Animals were randomly divided into six groups of 12 mice each, including: Control group, three groups separately treated respectively with 100, 200, and 400mg/kg hydroethanolic R. communis seed extract, morphine (1mg/kg)-treated group, and naloxone (0.1mg/kg) + R. communis seed extract (200mg/kg)-treated group. All animals received extract and drugs intraperitoneally. To evaluate the analgesic effect of the extract, writhing and tail flick tests were used. The 200 and 400mg/kg of the extract significantly increased pain threshold compared to the control group in writhing and tail flick tests (P<0.01). Moreover, 400mg/kg of the extract showed a stronger antinociceptive effect especially in writhing test compared to the control and other treated groups (P<0.001). Analgesic effects of hydroethanolic R. communis seed extract observed in the tail flick and writhing tests are probably related to activation of opioid system. Results may suggest that this plant extract might be beneficial in relieving human pain.

RESUMO: A dor é um sentido com efeitos essencialmente protetores. Ouso de drogas químicas e plantas medicinais é um método convencional para gerenciar a dor, no entanto, seus efeitos colaterais têm causado uma maior tendência para o uso de ervas medicamentosas entre os pacientes. Este estudo nos levou a investigar as ações antinociceptivas do extrato de sementes de Ricinus communis (RCE) em camundongos machos. Neste estudo experimental, foram utilizados 72 camundongos machos com peso de 25±30gr. Os animais foram divididos aleatoriamente em seis grupos de 12 cada: grupo controle, três grupos tratados separadamente com 100, 200 e 400mg/kg de extrato de sementes de R. communis hidroetanolico, grupo tratado com morfina (1mg/kg) e naloxona (0,1mg/kg) + R. Grupo tratado com extrato de semente de communis (200mg/kg). Para avaliar o efeito analgésico do extrato, utilizaram-se testes de contorção e cauda. Os dados foram analisados pela ANOVA e pelo teste de Tukey. P<0,05 foi considerado estatisticamente significante. Dose de 200 e 400mg/kg de extrato aumentou significativamente o limite de dor em comparação com o grupo controle em testes de retorção e cauda (P<0,01). Além disso, 400mg/kg de extracto apresentaram efeito antinoceptivo mais forte especialmente no teste de contorção em comparação com o controle e outros grupos tratados (P <0,001). Os efeitos analgésicos do extrato de semente de R. communanolanol foram observados no teste da cauda e nos testes de contorção. Este efeito provavelmente está relacionado à ativação do sistema opioide.