ABSTRACT
EGb761 is a well-defined mixture of active compounds extracted from Ginkgo biloba leaves. This extract is used clinically due to its neuroprotective effects, exerted probably via its potent antioxidant or free radical scavenger action. Previous studies suggest that oxidative stress, via free radical production, may play an important role in depression and animal models for depression-like behavior. Preclinical studies have suggested that antioxidants may have antidepressants properties. The aim of this study was to investigate the antidepressant-like of EGb761 due to its antioxidant role against oxidative stress induced in the forced swimming test, the most widely used preclinical model for assessing antidepressant-like behavior. Male BALB/c mice were pretreated with EGb761 (10mg/kg, ip) daily for 17 days followed by the forced swimming test and spontaneous locomotor activity. Animals were sacrificed to evaluate lipid peroxidation, different antioxidant enzyme activities, serotonin and dopamine content in midbrain, hippocampus and prefrontal cortex. EGb761 significantly decreased the immobility time (39%) in the forced swimming test. This antidepressant-like effect of EGb761 was associated with a reduction in lipid peroxidation and superoxide radical production (indicated by a downregulation of Mn-superoxide dismutase activity), both of which are indicators of oxidative stress. The protective effect of EGb761 is not related to excitatory or inhibitory effects in locomotor activity, and was also associated with the modulation of serotonergic and dopaminergic neurotransmission. It is suggested that EGb761 produces an antidepressant-like effect, and that an antioxidant effect against oxidative stress may be partly responsible for its observed neuroprotective effects.
Subject(s)
Antidepressive Agents/pharmacology , Oxidative Stress/drug effects , Plant Extracts/pharmacology , Swimming/psychology , Animals , Blotting, Western , Dopamine/metabolism , Ginkgo biloba , Glutathione Peroxidase/metabolism , Glutathione Reductase/metabolism , Hippocampus/drug effects , Hippocampus/metabolism , Lipid Peroxidation/drug effects , Male , Mesencephalon/drug effects , Mesencephalon/metabolism , Mice , Mice, Inbred BALB C , Motor Activity/drug effects , Prefrontal Cortex/drug effects , Prefrontal Cortex/metabolism , Serotonin/metabolism , Superoxide Dismutase/metabolism , Synaptic Transmission/drug effectsABSTRACT
The endogenous peptide nociceptin (orphanin FQ) plays a role in several important physiological functions in the CNS such as pain, anxiety and locomotion. It has previously been found that injection of 10 nmol nociceptin into the CA3 region of the hippocampus markedly impairs spatial learning and memory in the rat. The present study examined the effects of lower doses of nociceptin (3.3, 1, 0.33 and 0.1 nmol/rat) on spatial learning. The 3.3 nmol dose impaired spatial learning over the 5 days of training although the effect was not as strong as with 10 nmol. In contrast, the two lower doses, 1 and 0.33 nmol/rat, improved spatial learning whereas the lowest dose, 0.1 nmol/rat, had no significant effect. Both the impairing and facilitating effect of nociceptin could be blocked by an ORL-1 receptor antagonist, [Phe1Psi(CH(2)-NH)Gly2]NC(1-13)NH2 (10 nmol/rat), indicating that both effects are ORL-1 receptor-mediated. The 3.3 nmol dose of nociceptin did not impair the performance in the visual platform task and did not alter swim speed or motor activity indicating no effects on motivation or motor performance. Taken together, these results show that nociceptin has a biphasic dose-effect curve and provide further evidence for a role of this neuropeptide in cognitive processes in the hippocampus.
