Abstinence following intermittent methylphenidate exposure dose‐dependently modifies brain glucose metabolism in the rat brain

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.

Exercise Modifies the Brain Metabolic Response to Chronic Cocaine Exposure Inhibiting the Stria Terminalis

“…Statistical analysis: PET image analysis was conducted as previously described [55,74,75]. Briefly, scans were reconstructed using the MAP algorithm (15 iterations, 0.01 smoothing, 256 × 256 × 256 resolution) [76].…”

Exercise Influences the Brain’s Metabolic Response to Chronic Cocaine Exposure in Male Rats

“…Analysis was conducted as previously described [6,49,50]. The scans were reconstructed using the MAP algorithm (15 iterations, 0.01 smoothing, 256 × 256 × 256 resolution).…”

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

“…The effect of chronic MP use on neuromorphology has been previously examined [105]. Briefly, adolescent male rats were treated with either water or a low dose of MP (4 mg/kg MP for the first hour and 10 mg/kg MP for the remaining 7 h of the 8 h treatment time) or a high-dose MP (30 mg/kg MP for the first hour and 60 mg/kg MP for the remaining 7 h).…”

“…After 3 months of daily treatment, some rats underwent 9.4T structural MRI. Imaging results concluded that chronic oral MP use with either dose decreased the brain volume of the posterior white matter in areas such as the cingulum bundle, dorsal hippocampal commissure, and the external capsule [105]. More specifically, in the corpus callosum/external capsule, chronic MP results in a 11-13% volume decrease (Table 6).…”