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 43 higher doses of drugs were required a s estimated according to the relationship D human =D animal (W human /W animal ) 0.7 where D=dose of drug in milligrams and W=body weight in kilograms. Ecstasy tablets h ave been reported to generally contain between 80 and 250mg of MDMA, and 2 to 3 tablets are typically taken together. 3 Based on this knowledge, the doses selected for the mice were approximately equivalent to an acute dose of 391mg and 1,174mg in a 70kg human or 5.610 - 3 mg/kg and 1.610 - 2 mg/kg. Due to the much slower elimination of MDMA in humans, our scientific rationale was to administer higher doses the mice. 45 We selected the oral route for our study because MDMA is typically taken by mouth in humans. Vehicle (0.9% NaCl) was administered alone to the mice in the control group. Diet. For the induction of dietary caloric restriction, we used the IF protocol in this study. 46,50 Mice were weighed and divided in four groups; AL treatment, AL control, IF treatment, and IF control. The mice were put on either an AL or IF diet at eight weeks of age with a weight of about 20 to 25g. The AL group mice had free access to food, while the IF group mice were maintained under an alternate day feeding schedule (allowed access to food AL every other day) for five weeks. 47 Both groups were fed with a standard laboratory mouse chow. For the IF groups, food was added or removed at 8am, and the animals were weighed every week. Previous studies have shown that rodents fed on IF protocol will consume 30 to 40 percent less calories over time compared to AL rodents, and have about 20-percent reduction of body weight. 48,49 We begain our experiments after about five weeks of maintaining the mice on their regimens, with a weight difference of about 25 to 30 percent less in the IF (26.1±2.3g) group compared to the AL group (36.4±4.1g). Food was withdrawn from mice in AL and IF groups six FIGURE 4.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). ^Significant difference between AL C and IF C groups.(^^^ p < 0.001) *Significant difference between the IF and AL groups (20 mg/kg).(*** p< 0.001) #Significant difference between the IF and AL groups (60 mg/kg).(### p <0.001) ★Significant difference between the IF C and IF groups (20 and 60 mg/kg).(p< 0.001) ★★Significant difference between the AL C and AL groups (20 and 60 mg/kg).(p< 0.001) 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). ^Significant difference between AL C and IF C groups. (^^^ p < 0.001) *Significant difference between the IF and AL groups (20 mg/kg). (*** p< 0.001) #Significant difference between the IF and AL groups (60 mg/kg). (### p <0.001) ★Significant difference between the AL C and AL (20 and 60 mg/kg).(*** p < 0.001) ★★Significant difference between the IF C and IF (20 and 60 mg/kg).(### p < 0.001)

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