Molecular and Neurochemical Effects of Methylphenidate on the Developing Brain
type: CreativeWork
description: Attention deficit hyperactivity disorder (ADHD) affects 2.6-4.5% of the worlds population, with affected children often performing poorly at school. The catecholamine hypothesis of ADHD proposes that the disorder results from a hypofunction of the fronto-striato-cerebellar catecholaminergic (i.e. dopaminergic and noradrenergic) system. However, abnormalities in the glutamatergic and GABAergic systems have also been implicated in the symptoms of ADHD. In addition, previous reports indicate that a deviation from the common pattern of cerebral lateralisation also contribute to some of the symptoms of ADHD, with under-activation of the right prefrontal and right parietal cortices observed in ADHD patients. The psychostimulant, methylphenidate (MPH) is the preferred drug for the treatment of the disorder, however the long-term consequences of the drug are not yet established. Here, we have investigated the effects of acute and chronic MPH treatment on monoaminergic protein markers, genes and their corresponding proteins involved in synaptic plasticity, as well as the drug’s effect on metabolic pathways. The investigations were conducted on brain regions implicated in the symptoms of ADHD in adolescent rats. Our data shows in Chapter 3 that MPH increases whole tissue and extracellular dopamine levels in the frontal cortex and striatum. Interestingly, this effect was more prominent in the left sides of these brain areas. Chronic MPH treatment also upregulated dopamine (DAT) and noradrenaline (NET) transporters in the striatum and the nucleus accumbens, an effect that could limit the long-term effectiveness of the drug, as larger doses may be required to reach a functional blockade of the upregulated transporters and achieve clinical efficacy. In addition, chronic MPH but not acute treatment increased protein expression of the: vesicular monoamine transporter (VMAT2), dopamine D1 receptor, and the catecholamine rate-limiting enzyme tyrosine hydroxylase (TH), in most of the …
abstract: Attention deficit hyperactivity disorder (ADHD) affects 2.6-4.5% of the worlds population, with affected children often performing poorly at school. The catecholamine hypothesis of ADHD proposes that the disorder results from a hypofunction of the fronto-striato-cerebellar catecholaminergic (i.e. dopaminergic and noradrenergic) system. However, abnormalities in the glutamatergic and GABAergic systems have also been implicated in the symptoms of ADHD. In addition, previous reports indicate that a deviation from the common pattern of cerebral lateralisation also contribute to some of the symptoms of ADHD, with under-activation of the right prefrontal and right parietal cortices observed in ADHD patients. The psychostimulant, methylphenidate (MPH) is the preferred drug for the treatment of the disorder, however the long-term consequences of the drug are not yet established. Here, we have investigated the effects of acute and chronic MPH treatment on monoaminergic protein markers, genes and their corresponding proteins involved in synaptic plasticity, as well as the drug’s effect on metabolic pathways. The investigations were conducted on brain regions implicated in the symptoms of ADHD in adolescent rats. Our data shows in Chapter 3 that MPH increases whole tissue and extracellular dopamine levels in the frontal cortex and striatum. Interestingly, this effect was more prominent in the left sides of these brain areas. Chronic MPH treatment also upregulated dopamine (DAT) and noradrenaline (NET) transporters in the striatum and the nucleus accumbens, an effect that could limit the long-term effectiveness of the drug, as larger doses may be required to reach a functional blockade of the upregulated transporters and achieve clinical efficacy. In addition, chronic MPH but not acute treatment increased protein expression of the: vesicular monoamine transporter (VMAT2), dopamine D1 receptor, and the catecholamine rate-limiting enzyme tyrosine hydroxylase (TH), in most of the …
author: Quansah, Emmanuel
license: https://dora.dmu.ac.uk/bitstreams/a8c86f04-1336-4bbb-a2b2-5e44ec43e4d7/download
date published: 2017-01
date modified: 2026-07-24T06:18:47Z
provider: De Montfort University
publisher: Networked Digital Library of Theses and Dissertations
type: WebPage
source organization: De Montfort University