Article

Dopamine vs Noradrenaline: Inverted-U Effects and ADHD Theories

School of Psychiatry, University of New South Wales,, Prince of Wales Hospital, Randwick, New South Wales, Australia.
Australian and New Zealand Journal of Psychiatry (Impact Factor: 3.41). 03/2009; 43(2):101-8. DOI: 10.1080/00048670802607238
Source: PubMed

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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    • "However, it appears that neither NE nor DA can act independently without affecting the other system. Both the NE and DA systems are required for proper operation of prefrontal functions because a selective impairment in either transmission within the PFC leads to disrupted working memory (Arnsten, 2004; Arnsten and Jin, 2014; Brozoski et al., 1979; Levy, 2009; Ramos and Arnsten, 2007; Vijayraghavan et al., 2007; Williams and Goldman-Rakic, 1995). Previous studies have also shown that both NE and DA levels undergo moderate and comparably sustained increases during a delayed alternation task in trained animals (Rossetti and Carboni, 2005), and DA may be taken up through the NE transporter (NET) in brain regions with low levels of DA transporter (DAT), such as PFC (Moron et al., 2002; Sesack et al., 1998). "
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    ABSTRACT: Among the neuromodulators that regulate prefrontal cortical circuit function, the catecholamine transmitters norepinephrine (NE) and dopamine (DA) stand out as powerful players in working memory and attention. Perturbation of either NE or DA signaling is implicated in the pathogenesis of several neuropsychiatric disorders, including attention deficit hyperactivity disorder (ADHD), post-traumatic stress disorder (PTSD), schizophrenia, and drug addiction. Although the precise mechanisms employed by NE and DA to cooperatively control prefrontal functions are not fully understood, emerging research indicates that both transmitters regulate electrical and biochemical aspects of neuronal function by modulating convergent ionic and synaptic signaling in the prefrontal cortex (PFC). This review summarizes previous studies that investigated the effects of both NE and DA on excitatory and inhibitory transmissions in the prefrontal cortical circuitry. Specifically, we focus on the functional interaction between NE and DA in prefrontal cortical local circuitry, synaptic integration, signaling pathways, and receptor properties. Although it is clear that both NE and DA innervate the PFC extensively and modulate synaptic function by activating distinctly different receptor subtypes and signaling pathways, it remains unclear how these two systems coordinate their actions to optimize PFC function for appropriate behavior. Throughout this review, we provide perspectives and highlight several critical topics for future studies.
    Full-text · Article · Jan 2016 · Brain research
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    • "COMT and PRODH enzymes are related to neurotransmitters, such as dopamine, noradrenaline, GABA, and glutamate, which play a role in the etiology of various psychiatric disorders323334. Hyperprolinemia causes microdeletions in chromosomal region 22q11[35,36], and deletion in this region was investigated in schizophrenia293031. It has been suggested that there may be an association between the PRODH enzyme and schizophrenia[37]. "
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    • "Moreover, decreased working memory (e.g. SWM) (Barkley, 1997; Gallagher and Blader, 2001; McLean et al., 2004; Dowson et al., 2004; Rodriguez-Jimenez et al., 2006; Levy, 2009) and difficulties in executive functioning (Seidman et al., 1998; Mercugliano, 1999; McLean et al., 2004; Rodriguez-Jimenez et al., 2006; Greene et al., 2008) are often reported. At a neurobiological level, due to the ameliorating effect of stimulant medications (e.g. "
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