The control of responsiveness in ADHD by catecholamines: evidence for dopaminergic, noradrenergic and interactive roles

Abstract

We explore the neurobiological bases of attention deficit hyperactivity disorder (ADHD) from the viewpoint of the neurochemistry and psychopharmacology of the catecholamine-based behavioural systems. The contributions of dopamine (DA) and noradrenaline (NA) neurotransmission to the motor and cognitive symptoms of ADHD (e.g. hyperactivity, variable and impulsive responses) are studied in rodent and primate models. These models represent elements of the behavioural units observed in subjects with ADHD clinically, or in laboratory settings (e.g. locomotion, changed sensitivity/responsivity to novelty/reinforcement and measures of executive processing). In particular, the models selected emphasize traits that are strongly influenced by mesocorticolimbic DA in the spontaneously hypertensive (SHR) and the Naples high excitability (NHE) rat lines. In this context, the mode of action of methylphenidate treatment is discussed. We also describe current views on the altered control by mesolimbic catecholamines of appropriate and inappropriate goal-directed behaviour, and the tolerance or intolerance of delayed reinforcement in ADHD children and animal models. Recent insights into the previously underestimated role of the NA system in the control of mesocortical DA function, and the frontal role in processing information are elaborated.

The −1021 C/T DBH polymorphism is associated with neuropsychological performance among children and adolescents with ADHD

“…Different studies evidenced decreased DA release and deficient inhibitory control over NE terminals, revealing a hypodopaminergic and hypernorepinephric profile for the SHR [Russell, 2002]. Mice knockout for the DBH gene presented more differences in DA than in NE levels, highlighting the importance of the DA/NE ratio [Oades et al, 2005]: although absent in the PFC of À/À mice, NE was only slightly decreased in þ/À animals, whereas DA levels were increased five and twofold respectively [Bourdelat-Parks et al, 2005]. This is in accordance with the model proposed by Cubells and Zabetian [2004], in which lower levels of DbH protein may lead to elevated ratios of DA to NE.…”

Different Locomotor Activities and Monoamine Levels in the Brains of Djungarian Hamsters (D. sungorus) and Roborovskii Hamsters (D. roborovskii)

“…These enzymes influence catecholamine and 5-HT levels in the brain [4]. In fact, different expressions of TH in some ADHD model animals were observed compared with normal animals [11]. The differences of monoamine levels in the whole brain between Djungarian and Roborovskii hamsters may be caused by differences in expression level or activity of these enzymes.…”

Developmental Effects of Selective Breeding for an Infant Trait

“…Various forms of perinatal insults are known to affect social behavior in rats (Berger et al, 2002;Gerardin et al, 2005;Muneoka & Takigawa, 2002;Muneoka, Nakatsu, Fuji, Ogawa, & Takigawa, 1999;Muneoka, Ogawa, & Kamei, 1997;Oades et al, 2005;Sullivan, 2004;Sullivan & Brake, 2003). For example, rats that have suffered perinatal malnutrition, or have been reared without access to play partners also show similar patterns of social reactivity and inability to communicate socially (Whatson & Smart, 1978;Whatson, Smart, & Dobbing, 1975;Whatson, Smart, & Dobbing, 1976).…”