Dopamine vs noradrenaline: inverted-U effects and ADHD theories.
ABSTRACT The aim of the present study was to review the dopamine theory of attention-deficit-hyperactivity disorder (ADHD), in light of recent use of noradrenergic therapies. A historical review of pharmacological theories of ADHD was conducted, including inverted-U, spatial working memory and neural circuit aspects. Pharmacological advances, including animal and human studies of dopaminergic and noradrenergic mechanisms at the prefrontal cortex (PFC), indicate that alpha-2A adrenoreceptor stimulation results in increased dendritic firing during delay periods for preferred directions, while moderate levels of D1 receptor stimulation result in reduction of delay-related firing to non-preferred directions, allowing representational control in the PFC. Recent studies of the COMT val/met gene and stimulant medication response may help explain variation in inverted-U responses in individuals. Further studies utilizing delay-related firing paradigms should be useful in the investigation of attentional syndromes, and responses to newer pharmacological treatments.
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ABSTRACT: Hyperactivity related behaviors as well as inattention and impulsivity are regarded as the nuclear symptoms of attention-deficit/hyperactivity disorder (ADHD).PLoS ONE 10/2014; 9(10):e108918. DOI:10.1371/journal.pone.0108918 · 3.53 Impact Factor
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ABSTRACT: This review examines molecular genetic studies shown to be of importance in the etiology of attention-deficit/hyperactivity disorder (ADHD) and contrasts prefrontal versus sub-cortical mechanisms. Although these mechanisms are not completely dissociated, an understanding of prefrontal dopaminergic/noradrenergic versus subcortical D1/D2 receptor mechanisms is useful for studies of diagnosis versus potential adverse effects. Dopamine physiology, dopamine receptor studies, alpha-2 agonist studies, and dopamine transporter and potential new therapies are reviewed. Further understandings of molecular mechanisms involved in etiology versus treatment and adverse effects should help personalize the treatment of ADHD.Pharmacogenomics and Personalized Medicine 01/2014; 7:349-56. DOI:10.2147/PGPM.S52844
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ABSTRACT: Our previous study showed enhanced declarative memory consolidation after acute methylphenidate (MPH) administration. The primary aim of the current study was to investigate the duration of this effect. Secondary, the dopaminergic contribution of MPH effects, the electrophysiological correlates of declarative memory, and the specificity of memory enhancing effects of MPH to declarative memory were assessed. Effects of 40mg of MPH on memory performance were compared to 100mg of levodopa (LEV) in a placebo-controlled crossover study with 30 healthy volunteers. Memory performance testing included a word learning test, the Sternberg memory scanning task, a paired associates learning task, and a spatial working memory task. During the word learning test, event-related brain potentials (ERPs) were measured. MPH failed to enhance retention of words at a 30min delay, but it improved 24h delayed memory recall relative to PLA and LEV. Furthermore, during encoding, the P3b and P600 ERP latencies were prolonged and the P600 amplitude was larger after LEV compared to PLA and MPH. MPH speeded response times on the Sternberg Memory Scanning task and improved performance on the Paired Associates Learning task, relative to LEV, but not PLA. Performance on the Spatial working memory task was not affected by the treatments. These findings suggest that MPH and LEV might have opposite effects on memory.European neuropsychopharmacology: the journal of the European College of Neuropsychopharmacology 10/2013; DOI:10.1016/j.euroneuro.2013.09.009 · 3.68 Impact Factor