RESUMO
Accumulating evidence indicates that the brain-gut peptide ghrelin which is expressed in hippocampus improves memory and learning processes. The MK-801, a noncompetitive NMDA receptor antagonist, has also shown amnesic properties in animal model. The current study was to find out whether intracerebroventricular administration of ghrelin can prevent amnesia induced by MK-801 in rats. A week after the surgery, during which cannuals were implanted in the lateral ventricular, the animals were trained and tested in a step-through type passive avoidance task. Memory retrieval was measured by step-through latency (STL) and total time in dark compartments (TDC). In the first series of experiments, we established a dose-response relationship for ghrelin on the passive avoidance paradigm. In the second set of experiments, animals were divided to two groups. In the first group, MK-801 (0.075, 0.15 and 0.3mg/kg) was injected intraperitoneally (i.p.) immediately after the acquisition session and in the second group MK-801 (same doses) was injected (i.p.) 30 min before the retention session. Analysis of data showed that in both groups, MK-801 impaired learning and memory. In the third set of experiments, administration of ghrelin (200 ng/rat) right after the acquisition session (i.e. before MK-801 injection) improved the MK-801 induced memory impairment, but administration of ghrelin before retrieval session did not affect the MK-801 induced memory impairment. These results show an interaction between ghrelin and glutamatergic system. A novel finding in this study is that ghrelin can prevent amnesia produced by NMDA antagonist in rats when injected in post-training phase.
Assuntos
Amnésia/prevenção & controle , Grelina/administração & dosagem , Amnésia/induzido quimicamente , Animais , Aprendizagem da Esquiva/efeitos dos fármacos , Maleato de Dizocilpina , Relação Dose-Resposta a Droga , Grelina/fisiologia , Injeções Intraventriculares , Masculino , Ratos , Ratos Wistar , Receptores de N-Metil-D-Aspartato/metabolismo , Retenção Psicológica/efeitos dos fármacosRESUMO
OBJECTIVE: Nitric oxide is a neural messenger molecule in the central nervous system that is generated from L-arginine via the nitric oxide synthase (NOS) and is involved in many important oplold-induced effects. In Iranian ancient medicine, Cuminum cyminum L (green seed) has been used for the treatment of some diseases. In the present study, the effect of intraperitoneal (ip) administration of different doses of cumin fruit essential oil (FEO) on the acquisition of morphine-induced conditioned place preference (GPP) in L-arginine-treated mice was investigated. METHODS: A total of 213 adult male albino Wistar mice were used in these experiments. The CPP paradigm was carried out in 5 continuous days, pre-conditioning, conditioning and post-conditioning. Animals were randomly assigned to one of the two groups for place conditioning. CPP was induced by subcutaneous (sc) injection of morphine (5 mg/kg) in 3 days conditioning schedule. On the test day, conditioning scores and locomotor activity were recorded by Ethovision software. RESULTS: Sole administration of different doses of cumin FEO (0.01%, 0.1%, 0.5%, 1% and 2%; lp) or L-arginine (50, 100 and 200 mg/kg; lp) during the CPP protocol could not induce CPP. Nonetheless, morphine-induced CPP was decreased by different doses of cumin FEO (0.01%-2%), whereas it was increased by L-arginine (50-200 mg/kg) when they were injected before morphine (5 rug/kg) during a 3-day conditioning phase (acquisition period). Additionally, cumin FEO could interestingly attenuate the raising effect of L-arginine on morphine-induced CPP in a dose-dependent manner. CONCLUSIONS: It is suggested that some components of the Cuminum cyminum L. seed attenuate the excessive effect of L-arginine on morphine-induced CPP through the NOS inhibitory mechanism. It seems that cumin FEO possibly acts as a NOS inhibitor.