Advances in the Pharmacotherapy of Attention-Deficit/Hyperactivity Disorder
Duke University, Durham, North Carolina, United StatesBiological Psychiatry (Impact Factor: 10.26). 12/2007; 62(9):951-3. DOI: 10.1016/j.biopsych.2007.08.009
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- "Dopamine and other neurotransmitters play a crucial role in the human neural system functioning affecting learning abilities, memory, cardiovascular systems and behavior   . The normal level of dopamine concentration in blood is about 10 −8 M and significant deviations from this value are observed in various pathologies like schizophrenia and Parkinson's disease    . This is why reliable dopamine sensing constitutes extremely important practical task. "
ABSTRACT: Advantages and disadvantages of voltammetric vs. potentiometric sensing of dopamine are discussed. The study is focused on the measurements in small sample volumes, rather than on the selectivity to dopamine. For the potentiometric sensing, a novel flow-through tubular unit is developed. For voltammetric measurements with bare gold and platinum electrodes, miniature cylinder cells with the volume of 200 mu l are developed. The CV and impedance data suggest that the dopamine diffusion to the electrode surface is the limiting stage of the whole electrode process which hinders measurements without stirring. It is shown that use of micro electrode arrays allows overpassing this limitation.
- "DA inputs to the forebrain originate from cell bodies located in the substantia nigra zona compacta and ventral tegmental area (see Fig. 2A) giving rise to the nigrostriatal , mesolimbic and mesocortical systems (Dahlstroem et al., 1964). Based on the clinical efficacy of stimulant drugs that boost brain DA function it is axiomatic to postulate that DA plays a significant role in the aetiology and treatment of impulsivity symptoms in ADHD (Solanto et al., 2001; Kollins and March, 2007; Swanson and Volkow, 2009). Research in animals supports this view. "
Article: Dopamine, serotonin and impulsivity[Show abstract] [Hide abstract]
ABSTRACT: Impulsive people have a strong urge to act without thinking. It is sometimes regarded as a positive trait but rash impulsiveness is also widely present in clinical disorders such as attention deficit hyperactivity disorder (ADHD), drug dependence, mania, and antisocial behaviour. Contemporary research has begun to make major inroads into unravelling the brain mechanisms underlying impulsive behaviour with a prominent focus on the limbic cortico-striatal systems. With this progress has come the understanding that impulsivity is a multi-faceted behavioural trait involving neurally and psychologically diverse elements. We discuss the significance of this heterogeneity for clinical disorders expressing impulsive behaviour and the pivotal contribution made by the brain dopamine and serotonin systems in the aetiology and treatment of behavioural syndromes expressing impulsive symptoms.
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- "Stimulant medications, including amphetamine and methylphenidate, are a primary treatment option for ADHD (Kollins and March, 2007; Swanson and Volkow, 2009). Clinical studies have shown that these drugs are effective at reducing impulsivity in ADHD patients (Brown and Sleator, 1979; Malone and Swanson, 1993; Rapport et al., 1988; Solanto et al., 2001); in addition, methylphenidate also decreases impulsive choice in non- ADHD adult participants (Pietras et al., 2003). "
ABSTRACT: Impulsivity is one of the core symptoms of attention-deficit/hyperactivity disorder (ADHD). The spontaneously hypertensive rat (SHR), a putative animal model of ADHD, has been used to investigate the neurobiology of impulsivity, although this model has been questioned over concerns that use of Wistar-Kyoto rats (WKY) as a comparison strain may exaggerate effects. The present study compared SHR, WKY and standard, outbred Sprague-Dawley (SD) rats on a delay discounting task where the primary measure was mean adjusted delay (MAD), or the indifference point (in sec) between choice of an immediate delivery of 1 grain-based pellet versus 3 pellets delivered after varying delays. The acute dose effects of the ADHD medications amphetamine (0.1-1.0 mg/kg) and methylphenidate (1.0-10 mg/kg) were then determined; in addition, the effect of the dopamine receptor antagonist fluphenazine (0.1-1.0 mg/kg) was also assessed for comparison with the indirect agonists. While there were no strain differences in the rate of task acquisition or stabilization of baseline MAD scores, SHR had significantly lower MAD scores than WKY but not SD due to the greater individual variability of MAD scores in SD. Although amphetamine did not alter MAD scores in any strain, methylphenidate selectively increased MAD scores in WKY and fluphenazine selectively increased MAD scores in SHR. WKY were also more sensitive than SHR and SD to the response-impairing effects of each drug. The finding that SHR showed a decrease in impulsivity following fluphenazine, but not following either amphetamine or methylphenidate, suggests that delay discounting in SHR may not represent a valid predictive model for screening effective ADHD medications in humans.
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