Advances in the Pharmacotherapy of Attention-Deficit/Hyperactivity Disorder

Duke University, Durham, North Carolina, United States
Biological Psychiatry (Impact Factor: 10.26). 12/2007; 62(9):951-3. DOI: 10.1016/j.biopsych.2007.08.009
Source: PubMed
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    • "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. "
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    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.
    Neuroscience 04/2012; 215(26):42-58. DOI:10.1016/j.neuroscience.2012.03.065 · 3.36 Impact Factor
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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). "
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    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.
    Brain research 06/2011; 1396:45-53. DOI:10.1016/j.brainres.2011.04.040 · 2.84 Impact Factor
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    ABSTRACT: Although stimulants as the treatment of choice are widely prescribed in ADHD, little is known about their long-term neurobiological effects. Hence, for the first time the present study examined the long-term effects of chronic methylphenidate (MPH) administration on striatal 5-hydroxytryptamine transporter (5-HTT) densities in an animal model of ADHD. First, it compared the normal development of striatal 5-HTT densities of spontaneously hypertensive rats (SHR) as an animal model of ADHD and Wistar Kyoto (WKY) rats as controls; binding of the highly selective ligand of 5-HTT [(3)H]paroxetine was determined on membrane preparations of the striatum of SHR and WKY rats on postnatal days 25, 50, and 90, i.e. from the time of weaning until adulthood. Second, the long-term effect of chronic administration of 2 mg/kg per day MPH at two different developmental stages (days 25-39 or 50-64) on the striatal 5-HTT density was examined in both rat strains at day 90. Long-term effects of MPH treatment on striatal 5-HTT density in adulthood could be ruled out in both healthy (WKY) and "ADHD" rats (SHR). But a higher striatal 5-HTT density in older SHR versus WKY rats might indicate ADHD specific changes in the 5-HT system that needs further investigation not only in animals.
    The World Journal of Biological Psychiatry 02/2009; 10(4 Pt 2):581-5. DOI:10.1080/15622970802653709 · 4.18 Impact Factor
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