Abstract
Methylphenidate (MPH) has been widely misused by children and adolescents who do not meet all diagnostic criteria for attention-deficit/hyperactivity disorder without a consensus about the consequences. Here, we evaluate the effect of MPH treatment on glucose metabolism and metabolic network in the rat brain, as well as on performance in behavioral tests. Wistar male rats received intraperitoneal injections of MPH (2.0mg/kg) or an equivalent volume of 0.9% saline solution (controls), once a day, from the 15th to the 44th postnatal day. Fluorodeoxyglucose-18 was used to investigate cerebral metabolism, and a cross-correlation matrix was used to examine the brain metabolic network in MPH-treated rats using micro-positron emission tomography imaging. Performance in the light-dark transition box, eating-related depression, and sucrose preference tests was also evaluated. While MPH provoked glucose hypermetabolism in the auditory, parietal, retrosplenial, somatosensory, and visual cortices, hypometabolism was identified in the left orbitofrontal cortex. MPH-treated rats show a brain metabolic network more efficient and connected, but careful analyses reveal that the MPH interrupts the communication of the orbitofrontal cortex with other brain areas. Anxiety-like behavior was also observed in MPH-treated rats. This study shows that glucose metabolism evaluated by micro-positron emission tomography in the brain can be affected by MPH in different ways according to the region of the brain studied. It may be related, at least in part, to a rewiring in the brain the metabolic network and behavioral changes observed, representing an important step in exploring the mechanisms and consequences of MPH treatment.
Highlights
Methylphenidate (MPH), a central nervous system (CNS) stimulant in use for approximately 70 years, is the drug of choice for pharmacological treatment of attention-deficit/hyperactivity disorder (ADHD) [1]
The current study was proposed to examine the effects of early chronic treatment with MPH on glucose metabolism and the metabolic network patterns in juvenile rat brain using microPET
We observed that rats treated with MPH have a more efficient and connected brain metabolic network between most of the evaluated regions, but the orbitofrontal cortex showed a loss of its connectivity with other areas of the brain
Summary
Methylphenidate (MPH), a central nervous system (CNS) stimulant in use for approximately 70 years, is the drug of choice for pharmacological treatment of attention-deficit/hyperactivity disorder (ADHD) [1]. Glucose is the main energy source for the brain; there is little information about the effects of MPH on glucose brain metabolism In this regard, Zhang and colleagues [45, 46] have demonstrated that microPET imaging is a very useful tool capable of distinguishing differences in retention of fluorodeoxyglucose-18 (18F-FDG) in the brains of rodent and the nonhuman primate treated chronically with MPH exploring the effects of this psychostimulant on aspects of brain function. We hypothesized that changes in brain glucose metabolism, metabolic network architecture and depressive-and anxiety-like behaviors may be involved in the MPH effects since their regulating may be modulated by dopaminergic neurotransmission, MPH's main target
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