Brief and extended abstinence from chronic oral methylphenidate treatment produces reversible behavioral and physiological effects

Abstract

Methylphenidate (MP) is a commonly prescribed psychostimulant to individuals with Attention Deficit Hyperactivity Disorder, and is often used illicitly among healthy individuals with intermittent breaks to coincide with breaks from school. This study examined how intermittent abstinence periods impact the physiological and behavioral effects of chronic oral MP self‐administration in rats, and whether these effects persist following prolonged abstinence from the drug. Rats were treated orally with water, low‐dose (LD), or high‐dose (HD) MP, beginning at PND 28. This daily access continued for three consecutive weeks followed by a 1‐week abstinence; after three repeats of this cycle, there was a 5‐week abstinence period. Throughout the study, we examined body weight, food intake, locomotor activity, and anxiety‐ and depressive‐like behaviors. During the treatment phase, HD MP decreased body weight, food intake, and depressive‐ and anxiety‐like behaviors, while it increased locomotor activity. During intermittent abstinence, the effects of MP on locomotor activity were eliminated. During prolonged abstinence, most of the effects of HD MP were ameliorated to control levels, with the exception of weight loss and anxiolytic effects. These findings suggest that intermittent exposure to chronic MP causes physiological and behavioral effects that are mostly reversible following prolonged abstinence.

Rosmarinus officinalis and Methylphenidate Exposure Improves Cognition and Depression and Regulates Anxiety-Like Behavior in AlCl3-Induced Mouse Model of Alzheimer’s Disease

“…Differences in dosage and treatment duration could be another possible reason for varying effects on anxiety (Zoratto et al, 2019). Although the physiological and behavioral effects of MPH are generally reversible after intermittent MPH chronic exposure, it is followed by prolonged abstinence (Kalinowski et al, 2020). However, withdrawal effects could also be the possible reason for high anxiety in the MPH-treated group in the present study.…”

Behavioral, Neurochemical and Developmental Effects of Chronic Oral Methylphenidate: A Review

“…Along with this, it has been demonstrated that there is a significant negative correlation between body weight and dark cycle circadian activity, and a positive correlation between dark cycle circadian activity and food intake [86]. MPinduced increases in locomotion were recorded during the dark cycle phase of circadian testing, during the hours when the subjects consumed MP, but not during the light cycle phase when they were deprived [83,85]. In terms of sleep, one study states that MP had no significant effect on multiple sleep parameters, but also states that this statistic may be due to their dosing schedule [14].…”

“…Sensitization is also examined throughout this testing and typically measured by monitoring the rat's floor plane (FP) moves (total number of start to stop movements), FP distance traveled, and FP velocity [14]. Results from rats using a two-bottle exposure method to MP showed that the FP moves, velocity, and distance traveled were significantly increased during weeks of treatment in comparison to the vehicle [14,83]. IP injection of MP also significantly increased distanced traveled and velocity [54].…”

“…This difference can be due to the differences in social stimuli used between male and female rats, with males being socialized with young rats to avoid aggression and female rats exposed to age and weight matched rats in the study [86]. It also remained clear that there is a significant difference between the high-dose MP group and water/low dose-treated groups throughout several of the studies [83].…”

“…Another study agreed with the significance of a high dose of MP in the FST and that the higher dose group spent less time in immobility. It also mentions that there is no significant difference between treatment groups during stages of abstinence [83].…”