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Published on: November 11, 2013
Abstinence following intermittent methylphenidate exposure dose-dependently modifies brain glucose metabolism in the
Eliz Arnavut1, John Hamilton1, Rutao Yao2
1Behavioral Neuropharmacology and Neuroimaging Laboratory on Addictions (BNNLA), Department of Pharmacology and Toxicology, Clinical Research Institute on Addictions, Jacobs School of Medicine and Biomedical Sciences, State University at Buffalo, Buffalo, New York.
Abstract:
Methylphenidate (MP) is a psychostimulant chronically prescribed for the treatment of attention deficit hyperactivity disorder (ADHD). Additionally, MP users may take breaks from using the medication during "drug holidays," which may include short-term or long-term breaks from medication. The present study utilized fluorodeoxyglucose (FDG) positron emission tomography (PET) to analyze the effects of chronic oral MP use and abstinence on brain glucose metabolism (BGluM) in rats at two different doses: high dose (HD) and low dose (LD). The schedule of treatment was 3 weeks on-treatment and 1 week off-treatment for a period of 13 weeks, followed by an abstinence period of 4 total weeks. Results showed that chronic MP treatment using this schedule did not lead to significant changes in BGluM when comparing the control to HD MP groups. However, significant activation in BGluM was observed after periods of abstinence between control and HD MP rats in the following brain regions: the trigeminal nucleus, reticular nucleus, inferior olive, lemniscus, mesencephalic reticular formation, inferior colliculus, and several areas of the cerebellum. These brain regions and functional brain circuit play a role in facial sensory function, the auditory pathway, organizing connections between the thalamus and cortex, motor learning, auditory function, control over eye movement, auditory information integration, and both motor and cognitive functions. These results, when considered with previous studies, indicate that MP schedule of use may have differing effects on BGluM. BGluM following long-term MP use was dependent on MP dose and schedule of use in rats. This study was conducted in non-ADHD model rats with the aim to establish an understanding of the effects of MP itself, especially given the growing chronic off-label and prescribed use of MP. Further studies are needed for analysis of the drug's effects on an ADHD model.
Insights
Chronic methylphenidate (MP) use did not alter brain glucose metabolism in rats. However, abstinence from MP revealed significant metabolic changes in brain regions involved in sensory and motor functions.
Area of Science:
- Neuroscience
- Pharmacology
- Medical Imaging
Background:
- Methylphenidate (MP) is a psychostimulant commonly prescribed for Attention Deficit Hyperactivity Disorder (ADHD).
- Patients may take intermittent breaks from MP, termed 'drug holidays,' involving short or long-term cessation.
- Understanding MP's effects on brain metabolism during continuous use and abstinence is crucial due to its widespread prescription and off-label use.
Purpose of the Study:
- To investigate the impact of chronic oral methylphenidate (MP) administration and subsequent abstinence on brain glucose metabolism (BGluM) in rats.
- To assess dose-dependent effects of MP on BGluM using high dose (HD) and low dose (LD) regimens.
- To explore the influence of a specific treatment schedule (3 weeks on, 1 week off) on brain metabolic activity.
Main Methods:
- Utilized fluorodeoxyglucose (FDG) positron emission tomography (PET) to measure BGluM in Sprague-Dawley rats.
- Administered MP orally following a cyclical schedule: 3 weeks of treatment followed by 1 week off, repeated for 13 weeks.
- Conducted a 4-week abstinence period post-treatment to evaluate metabolic recovery and changes.
Main Results:
- Chronic MP treatment, even at a high dose, did not induce significant changes in overall BGluM compared to control rats.
- Significant increases in BGluM were observed in specific brain regions after the abstinence period in HD MP rats versus controls.
- Affected regions included the trigeminal nucleus, reticular nucleus, inferior olive, lemniscus, mesencephalic reticular formation, inferior colliculus, and cerebellum, involved in sensory, auditory, motor, and cognitive functions.
Conclusions:
- The schedule and dose of methylphenidate (MP) significantly influence brain glucose metabolism (BGluM) during abstinence, not necessarily during continuous use.
- MP's long-term effects on BGluM are complex and depend on the dosing regimen and intermittent cessation.
- Further research is warranted to elucidate MP's effects in ADHD models and understand the long-term implications of its varied usage patterns.
