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. 2017 Feb 1;14(1-2):40-52.
eCollection Jan-Feb 2017.

Behavioral and Stereological Analysis of the Effects of Intermittent Feeding Diet on the Orally Administrated MDMA ("Ecstasy") in Mice

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Free PMC article

Behavioral and Stereological Analysis of the Effects of Intermittent Feeding Diet on the Orally Administrated MDMA ("Ecstasy") in Mice

Zeinab Ebrahimian et al. Innov Clin Neurosci. .
Free PMC article

Abstract

Background: 3,4-methylenedioxy-methamphetamine or MDMA (also known as "ecstasy" or "molly") is a commonly abused drug that affects behavior and can lead to neuronal damage. Intermittent feeding is an effective dietary protocol that promotes neuroprotection and improves behavioral outcomes in animal models of neurotoxicity and neurodegenerative diseases. In this study, we investigated the behavioral and histological outcomes of the effect of intermittent feeding on the orally administered MDMA in mice. Methods: The animals (male albino mice) were divided into four groups: ad libitum (AL), intermittent feeding (IF) (food given every other day), and AL and IF control groups. After five weeks, AL and IF groups were given a single oral dose of 20 or 60mg/kg MDMA. Behavior was assessed with the elevated plus-maze and the open field tests. Each of the treatment groups were then divided in to two groups: AL-AL (AL diet throughout), AL-IF (IF after MDMA administration), IF-IF (IF diet throughout), IF-AL (AL after MDMA administration). The second behavioral assessment was performed on ninth and 12th day after MDMA administration. The brains were then prepared with cresyl fast violet stain for stereology of the CA1 area of hippocampus. Results: The AL groups showed enhanced locomotion and anxiety compared to the IF (p<0.001); however, IF groups showed significantly (p<0.05) more locomotor activity and less anxiety recovery at ninth and 12th days compared to the AL animals. The neuronal numerical density was significantly (p<0.05) higher in the hippocampus in the AL-IF groups compared to the AL-AL. Conclusion: IF regimen can significantly modify various behavioral characteristics induced by MDMA and promotes faster recovery from MDMA's anxiogenic effects. Additionally, IF regimen had neuroprotective effects on the neurons of the CA1 area of the hippocampus after a single oral dose of MDMA. We believe the results of our study support the need for further research examining the behavior modifying and neuroprotective potential of the IF regminen for the treatment of drug addiction in humans.

Keywords: MDMA; elevated plus-maze; hippocampus; intermittent feeding; neuronal numerical density; open field.

Conflict of interest statement

FINANCIAL DISCLOSURES:The authors have no conflicts of interest relevant to the content of this article.

Figures

FIGURE 1.
FIGURE 1.
The experimental design of study
FIGURE 2.
FIGURE 2.
Time percentage spent in open arms (in seconds) of plus-maze of AL and IF groups, 30 minutes after MDMA gavage. Ad libitum (AL), Intermittent feeding (IF), Control (C).(Analysis was done by one-way ANOVA; significance was determined by post hoc Tukey test)
FIGURE 3.
FIGURE 3.
Time percentage spent in open arms (in seconds) of plus-maze AL-AL, AL-IF, IF-IF and IF-AL subgroups, 12 days after MDMA gavage. Ad libitum (AL), Intermittent feeding (IF), Control (C).(Analysis was done by pairwise comparison one-way ANOVA followed by post hoc Tukey test).
FIGURE 4.
FIGURE 4.
Locomotor activity in open field test (Total distance travelled in cm) between AL and IF groups during 60 minutes immediately after MDMA administration. Ad libitum (AL), Intermittent feeding (IF), Control (C). (Analysis was done by one-way ANOVA; significance was determined by post hoc Tukey test).
FIGURE 5.
FIGURE 5.
Rearing behavior in the open field (number) between AL and IF groups during 60 minutes immediately after MDMA administration. Ad libitum (AL), Intermittent feeding (IF), Control (C). (Analysis was done by one-way ANOVA; significance was determined by post hoc Tukey test).
FIGURE 6.
FIGURE 6.
Locomotor activity in open field test between AL-AL, AL-IF, IF-IF, IF-AL subgroups 9 days after MDMA administration. Ad libitum (AL), Intermittent feeding (IF), Control (C). (Analysis was done by one-way ANOVA; significance was determined by post hoc Tukey test).
FIGURE 7.
FIGURE 7.
Rearing behavior in the open field (number) of AL-AL, AL-IF, IF-IF and IF-AL subgroups, 12 days after MDMA gavage. Ad libitum (AL), Intermittent feeding (IF), Control (C).(Analysis was done by one-way ANOVA; significance was determined by post hoc Tukey test).
FIGURE 8.
FIGURE 8.
Numerical density (neuron/mm3) of hippocampal CA1 neurons of AL-AL, AL-IF, IF-IF and IF-AL subgroups. Ad libitum (AL), Intermittent feeding (IF), Control (C).(Analysis was done by one-way ANOVA; significance was determined by post hoc Tukey test). #Significant difference between the AL-AL and AL-IF subgroups (20 and 60 mg/kg).(### p < 0.001)
FIGURE 9.
FIGURE 9.
Numerical density of hippocampal CA1 neurons in AL-AL, AL-IF and AL control subgroups. Cresyl violet stain of 30 μ paraffin sections. Scale bar= 100 μm
FIGURE 10.
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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