Innovations In Clinical Neuroscience

JAN-FEB 2017

A peer-reviewed, evidence-based journal for clinicians in the field of neuroscience

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[ V O L U M E 1 4 , N U M B E R 1 – 2 , J A N U A R Y – F E B R U A R Y 2 0 1 7 ] Innovations in CLINICAL NEUROSCIENCE 47 effects have been previously studied in d ifferent strains of mice. These include effects on tau phosphorylation; monoamine assay; motor activity; electrocardiogram (ECG) abnormalities; neuronal degeneration in C57BL/6J; l ocomotor activity; exploratory behavior; anxiety; defensive behavior; neuronal damage in BALBC, DA, and 5-HT concentrations; hyperthermia; locomotor response in Swiss Webster; hyperactivity; social interaction; passive avoidance; anxiety and brain monoamines concentrations in OF1 mice; and free radical formation, lipid peroxidation, and neurodegeneration of DA nerve endings, locomotor activity, and hyperthermia in NIH/Swiss mice. 8–11,19,21,52,59,62,63 The IF diet is an effective method for neuroprotection and revival of the neuronal system and recovery of behavioral function in animal models of neurotoxicity and neurodegeneration. 28,39,41,49,64 Effect of IF on anxiety behavior in the EPM model. Anxiety influences animal behavior in different ways and causes mice to avoid places that entail risk. 65 The elevated plus-maze test is based on the assumption that in a state of anxiety the mice will have an aversion to heights and open spaces, preferring to spend more time in the closed arms rather than in the open arms of the maze. This model has been validated in mice, and it is useful for evaluation of anxiogenic-like and anxiolytic-like properties of drugs. 66 In the past decade, a large number of pharmacological studies on anxiety have been done with this model. There is good evidence for the neuropharmacological and neuroanatomical parallels between rodent emotionality and human anxiety. 12 Typical exploratory behavior in this test was in favor of the open arms; forced or voluntary entry into the close arms was associated with hormonal and behavioral changes that are indicative of anxiety. 12,53 Animals were re-tested at 12 days post-gavage to assess long-term anxiety levels. 55 In our study, when EPM test was carried out 30 minutes after the MDMA gavage, AL treatment groups showed a decrease in time spent in open arms compared to the AL control and IF groups, which indicated anxiety-like behavior. On the other hand, IF treatment groups showedan increase in time spent in open arms compared to the IF control and the AL groups, indicating anxiolytic-like behavior. When the EPM test was carried out 12 days after of MDMA gavage, subgroups that were under IF protocol showed less anxiety- like behavior than the AL subgroups. It is noteworthy that the anxiety-like behavior persisted in AL groups after 12 days of MDMA administration while animals in IF groups showed negligible signs of such behavior.This suggests that the IF diet had a reparative effect, leading to faster recovery from the MDMA toxicity and a quicker return to normal behavior. In previous studies, MDMA caused anxiety-like behavior in drug users. The consistency of human and animal observations confirms the notion that MDMA has anxiogenic-like effects. 12 Studies in mice also report similar effects of MDMA. 53 MDMA is an active releaser of neurotransmitters responsible for diverse behavioral effects. It has moderate affinities for a variety of receptor subtypes of neurotransmitter systems, including serotonin, dopamine, and noradrenaline, that play important roles in the neural processes that control anxiety. 12 One of the leading behavioral effects of the CR diet is a decrease in anxiety- like behavior, which was also observed in the mice. 67 The anxiolytic effects of IF are not due to a general decrease in calories or reductions in specific caloric elements, such as fat, protein, and carbohydrates, or vitamins and minerals. For example, a study of rats showed an anxiolytic-like effect that continued for 10 days after the normalization of feeding following 10 days of CR. 47 In various strains of mice, studies have shown that animals maintained on a CR diet display alterations in expression of receptors, neuropeptides, FIGURE 10. Numerical density of hippocampal CA1 neurons in IF-IF, IF-AL and IF C groups. Cresyl violet stain of 30 µ paraffin sections. Scale bar= 100 µm

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