Methylphenidate alleviates manganese-induced impulsivity but not distractibility
| Autor: | Barbara J. Strupp, Walter Uribe, Donald R. Smith, Myla Strawderman, Lauren Ysais, Stephane A. Beaudin |
|---|---|
| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Serial reaction time Male Impulsivity Dendritic spine Dendritic Spines Prefrontal Cortex Striatum Toxicology Basic Behavioral and Social Science Article 03 medical and health sciences Cellular and Molecular Neuroscience 0302 clinical medicine Developmental Neuroscience Behavioral and Social Science medicine Animals Attention Drug Interactions Young adult Prefrontal cortex Pediatric Manganese Methylphenidate Neurosciences Ritalin Attention Deficit Hyperactivity Disorder (ADHD) Corpus Striatum Impulse control Rats 030104 developmental biology Mental Health 5.1 Pharmaceuticals Impulsive Behavior Cognitive Sciences medicine.symptom Development of treatments and therapeutic interventions Psychology Neuroscience 030217 neurology & neurosurgery medicine.drug |
| Popis: | Recent studies from our lab have demonstrated that postnatal manganese (Mn) exposure in a rodent model can cause lasting impairments in fine motor control and attention, and that oral methylphenidate (MPH) treatment can effectively treat the dysfunction in fine motor control. However, it is unknown whether MPH treatment can alleviate the impairments in attention produced by Mn exposure. Here we used a rodent model of postnatal Mn exposure to determine whether (1) oral MPH alleviates attention and impulse control deficits caused by postnatal Mn exposure, using attention tasks that are variants of the 5-choice serial reaction time task, and (2) whether these treatments affected neuronal dendritic spine density in the medial prefrontal cortex (mPFC) and dorsal striatum. Male Long-Evans rats were exposed orally to 0 or 50 Mn/kg/d throughout life starting on PND 1, and tested as young adults (PND 107–115) on an attention task that specifically tapped selective attention and impulse control. Animals were treated with oral MPH (2.5 mg/kg/d) throughout testing on the attention task. Our findings show that lifelong postnatal Mn exposure impaired impulse control and selective attention in young adulthood, and that a therapeutically relevant oral MPH regimen alleviated the Mn-induced dysfunction in impulse control, but not selective attention, and actually impaired focused attention in the Mn group. In addition, the effect of MPH was qualitatively different for the Mn-exposed versus control animals across a range of behavioral measures of inhibitory control and attention, as well as dendritic spine density in the mPFC, suggesting that postnatal Mn exposure alters catecholaminergic systems modulating these behaviors. Collectively these findings suggest that MPH may hold promise for treating the behavioral dysfunction caused by developmental Mn exposure, although further research is needed with multiple MPH doses to determine whether a dose can be identified that ameliorates the dysfunction in both impulse control and selective attention, without impairing focused attention. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|