Impact of developmental exposure to methylphenidate on rat brain’s immune privilege and behavior: Control versus ADHD model

Autor: Vanessa Coelho-Santos, Filipa L. Cardoso, Carlos Fontes-Ribeiro, Ricardo A. Leitão, Ana P. Silva
Rok vydání: 2018
Předmět:
Male
0301 basic medicine
medicine.medical_specialty
Immunology
Prefrontal Cortex
Anxiety
Immune Privilege
Blood–brain barrier
medicine.disease_cause
Rats
Inbred WKY
03 medical and health sciences
Behavioral Neuroscience
0302 clinical medicine
Immune system
Immune privilege
Rats
Inbred SHR
Internal medicine
mental disorders
medicine
Animals
Attention deficit hyperactivity disorder
Attention
Prefrontal cortex
Neuroinflammation
Endocrine and Autonomic Systems
Methylphenidate
Brain
medicine.disease
Rats
Disease Models
Animal
030104 developmental biology
medicine.anatomical_structure
Endocrinology
Attention Deficit Disorder with Hyperactivity
Blood-Brain Barrier
Exploratory Behavior
Central Nervous System Stimulants
Psychology
human activities
Neuroscience
030217 neurology & neurosurgery
Oxidative stress
medicine.drug
Zdroj: Brain, Behavior, and Immunity. 68:169-182
ISSN: 0889-1591
Popis: Attention deficit hyperactivity disorder (ADHD) is the most prevalent childhood mental disorders that often persists into adulthood. Moreover, methylphenidate (MPH) is the mainstay of medical treatment for this disorder. Yet, not much is known about the neurobiological impact of MPH on control versus ADHD conditions, which is crucial to simultaneously clarify the misuse/abuse versus therapeutic use of this psychostimulant. In the present study, we applied biochemical and behavioral approaches to broadly explore the early-life chronic exposure of two different doses of MPH (1.5 and 5 mg/kg/day) on control and ADHD rats (Wistar Kyoto and Spontaneously Hypertensive rats, respectively). We concluded that the higher dose of MPH promoted blood-brain barrier (BBB) permeability and elicited anxiety-like behavior in both control and ADHD animals. BBB dysfunction triggered by MPH was particularly prominent in control rats, which was characterized by a marked disruption of intercellular junctions, an increase of endothelial vesicles, and an upregulation of adhesion molecules concomitantly with the infiltration of peripheral immune cells into the prefrontal cortex. Moreover, both doses of MPH induced a robust neuroinflammatory and oxidative response in control rats. Curiously, in the ADHD model, the lower dose of MPH (1.5 mg/kg/day) had a beneficial effect since it balanced both immunity and behavior relative to vehicle animals. Overall, the contrasting effects of MPH observed between control and ADHD models support the importance of an appropriate MPH dose regimen for ADHD, and also suggest that MPH misuse negatively affects brain and behavior.
Databáze: OpenAIRE
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