β2 Mediated inhibition of [3H]dopamine release from nucleus accumbens slices and monoamine levels in a rat model for attention-deficit hyperactivity disorder

Villiers, A. S. De; Russell, Vivienne A.; Sagvolden, Terje; Searson, A.; Jaffer, A.; Taljaard, J. J. F.

doi:10.1007/bf00973098

Cited by 67 publications

(43 citation statements)

References 33 publications

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“…The spontaneously hypertensive rat (SHR) has also been used as an animal model of ADHD because of the SHR's locomotor hyperactivity and impaired discriminative performance. Studies on the SHR implicate dopaminergic and noradrenergic systems de Villiers et al 1995;Papa et al 1998;King et al 2000) but do not support a simple theory of altered dopamine neurotransmission in ADHD. Structural brain imaging studies have shown abnormalities in the frontal lobe and subcortical structures (globus pallidus, caudate, corpus callosum), regions known to be rich in dopamine neurotransmission and important in the control of attention and response to organization (Lou et al 1990;Zametkin et al 1990;Rubia et al 1997).…”

mentioning

confidence: 87%

Dopaminergic System Genes in ADHD Toward a Biological Hypothesis

Kirley

Hawi

Daly

et al. 2002

Neuropsychopharmacology

107

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Converging evidence has implicated abnormalities of dopamine neurotransmission to the pathology of attention deficit hyperactivity disorder (ADHD).Attention Deficit Hyperactivity Disorder (ADHD) is a common condition of childhood affecting 3-6% of school age children worldwide (Barkley 1990), with males being affected three times more than females (Anderson et al. 1987; Baumgartel et al. 1995). Its core clinical features include excessive motor activity, impaired attention, and impulsivity. ADHD causes marked educational, social, and family difficulties for sufferers and their relatives. The condition is of early onset (usually before age 7) and tends to persist throughout childhood. Moreover, approximately 30-60% of children with ADHD have persisting psychopathology in adulthood (Gittelman et al. 1985;Weiss and Hechtman 1986; Barkley 1990;Swanson et al. 1998a). The exact etiology of ADHD is Received March 8, 2001; revised February 12, 2002; accepted February 20, 2002. Online publication: 2/28/02 at www.acnp.org/citations/ Npp022802254. 608 A. Kirley et al. N EUROPSYCHOPHARMACOLOGY 2002 -VOL . 27 , NO . 4 unknown, but a substantial genetic element exists. This has been demonstrated by family (Biederman et al. 1990(Biederman et al. , 1992Faraone et al., 1992Faraone et al., , 1994, twin (Thapar et al. 1995;Silberg et al. 1996;Levy et al. 1997), and adoption studies (Alberts-Corush et al. 1986; Cadoret and Stewart 1991). The heritability (h 2 ) of ADHD has been estimated to be .50-.98 (Gjone et al. 1996;Levy et al. 1997). The exact mode of transmission remains unknown. Segregation analyses (Morrison and Steward 1974;Deutsch et al. 1990, Faraone et al. 1992, Hess et al. 1995 have proposed models of inheritance from major gene effects through oligogenic to polygenic and multifactorial models, but the differences in statistical "fit" between multifactorial genetic models and single gene inheritance is modest. The multifactorial concept is consistent with ADHD's high population prevalence (2-7%), high concordance in monozygotic twins (68-81%), but modest recurrence risks to first-degree relatives.Dysregulation in catecholamine neurotransmission is implicated in the pathophysiology of ADHD (Faraone and Biederman 2002). The dopaminergic neurotransmitter system has been most extensively studied. This article will focus mainly on its role in the etiology of ADHD. Evidence to support dopaminergic dysfunction in ADHD derives from three research areas: the neuropharmacology of stimulant medication (Zametkin and Rapoport 1987; Amara and Kuhar 1993), the behavior and biochemistry of animal models (Giros et al. 1996;Gainetdinov et al. 1999, Russell 2000, and neuroimaging studies in ADHD adults (Dougherty et al. 1999, Krause et al. 2000, and Faraone and Biederman 2002. For this reason, many molecular genetic studies have focused on dopamine system genes.The gene encoding the dopamine transporter, DAT1, was the initial candidate gene studied. This gene is of particular interest, as the transporter is the principal target...

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mentioning

confidence: 87%

Dopaminergic System Genes in ADHD Toward a Biological Hypothesis

Kirley

Hawi

Daly

et al. 2002

Neuropsychopharmacology

107

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“…It is innervated by dopamine (DA) neurons that respond to errors in reward prediction in a manner appropriate for a teaching signal (Schultz, 1998;Schultz et al, 1997;Schultz & Dickinson, 2000;Schultz et al, 1998), as discussed above, and interventional studies have shown it to be a key site for the motivational impact of impending rewards (reviewed by , Everitt et al (1999), Parkinson, Cardinal, and Everitt (2000), Robbins et al (2005), Robbins and Everitt (1996), Salamone, Cousins, and Snyder (1997)). Acb abnormalities have also been observed in rat models of ADHD (Carey et al, 1998;de Villiers et al, 1995;Papa et al, 1996Papa et al, , 1998Russell et al, 1998;Russell, 2000;Sadile, 2000). Causal experimental studies have shown that lesions of the AcbC produce impulsive choice, reducing rats' preference for large/delayed rewards, compared to small/immediate rewards (Cardinal, Pennicott, Sugathapala, Robbins, & Everitt, 2001;Cardinal, Parkinson, et al, 2003).…”

Section: Choice Involving Delayed Reinforcementmentioning

confidence: 99%

“…Many of the inferences regarding the neural abnormalities in children with ADHD have been drawn from studies of the spontaneously hypertensive rat (SHR), an inbred strain of rat that serves as an animal model of ADHD (Russell et al, 2005;Sagvolden, 2000;Sagvolden et al, 1992;Sagvolden, Pettersen, & Larsen, 1993;Wultz, Sagvolden, Moser, & Moser, 1990). This rat exhibits pervasive hyperactivity and attention problems that resemble ADHD, exhibits a steeper 'scallop' of responding on fixed-interval schedules of reinforcement, which can be interpreted as abnormally high sensitivity to immediate reinforcement (Sagvolden et al, 1992), is impulsive on measures of 'execution impulsivity' (Evenden & Meyerson, 1999), and has a complex pattern of abnormalities in its DA system (Carey et al, 1998;de Villiers et al, 1995;Papa, Sagvolden, Sergeant, & Sadile, 1996;Papa, Sergeant, & Sadile, 1998;Russell, de Villiers, Sagvolden, Lamm, & Taljaard, 1998;Russell, Devilliers, Sagvolden, Lamm, & Taljaard, 1995;Russell, 2000).…”

Section: Psychostimulants and Impulsivitymentioning

confidence: 99%

Neural systems implicated in delayed and probabilistic reinforcement

2006

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This review considers the theoretical problems facing agents that must learn and choose on the basis of reward or reinforcement that is uncertain or delayed, in implicit or procedural (stimulus-response) representational systems and in explicit or declarative (action-outcome-value) representational systems. Individual differences in sensitivity to delays and uncertainty may contribute to impulsivity and risk taking. Learning and choice with delayed and uncertain reinforcement are related but in some cases dissociable processes. The contributions to delay and uncertainty discounting of neuromodulators including serotonin, dopamine, and noradrenaline, and of specific neural structures including the nucleus accumbens core, nucleus accumbens shell, orbitofrontal cortex, basolateral amygdala, anterior cingulate cortex, medial prefrontal (prelimbic/infralimbic) cortex, insula, subthalamic nucleus, and hippocampus are examined.

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“…For example, medetomidine has been shown to decrease dopamine outflow in the mouse striatum in a dose-dependent fashion – an effect that can be prevented by co-administration with atipamezole [44]. In addition, α 2 -antagonists have been shown to increase dopamine activity in the nucleus accumbens [45]. Infusion of atipamezole into the arcuate, therefore, may be promoting TIDA and THDA activity to suppress basal levels of PRL.…”

Section: Discussionmentioning

confidence: 99%

Infusion of Alpha-2-Adrenergic Agents into the Paraventricular and Arcuate Nuclei of the Hypothalamus in the Siberian Hamster: Opposing Effects on Basal Prolactin

Dodge¹,

Badura²

2002

Neuroendocrinology

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Although the α₂-adrenergic receptor subtype has been shown to have a significant influence on circulating levels of prolactin (PRL), its exact role remains unclear. A multitude of studies have demonstrated that blockade of the α₂-receptor can either elevate or decrease circulating levels of PRL. α₂-Receptor-mediated control of both stimulatory and inhibitory arms of the PRL regulatory system may explain this discrepancy. Activation of the α₂-receptor has been shown to inhibit the activity of its target cell, and therefore antagonism of the α₂-receptor within a stimulatory component (e.g., paraventricular nucleus (PVN) of the hypothalamus) would theoretically have the opposite effect that it would have within an inhibitory component (arcuate nucleus of the hypothalamus). Thus, the purpose of this study was to investigate the functional role of the α₂-adrenergic receptor in modulating circulating levels of PRL both at the level of the PVN and arcuate using reverse microdialysis of α₂-adrenergic agents coupled with serial blood sampling in the male Siberian hamster. Male hamsters were fitted with a jugular cannula for serial blood sampling, and an indwelling microdialysis probe for intrahypothalamic drug administration between 08:00 and 10:00 h. Blood samples were collected every hour for 5 h (12:00–17:00 h). During the third sampling period, atipamezole (α₂-antagonist) or medetomidine (α₂-agonist) at one of three doses were infused into the PVN or the arcuate to assess effects on basal PRL. At the level of the PVN, infusion of atipamezole initiated an increase in basal PRL in a dose-dependent fashion, whereas infusion of medetomidine induced a significant decline in basal PRL in a dose-dependent fashion. In the arcuate, only the highest dose of atipamezole had an effect on PRL, and this was in the opposite direction from that seen in the PVN. Infusion of medetomidine did not have a significant effect on basal PRL levels; however, a trend toward a significant elevation was observed for the highest dose. These results suggest that the α₂-receptor subtype may have opposite effects on circulating levels of PRL within the PVN and arcuate regions, and may explain why antagonism of the α₂-receptor has been shown to initiate both surges and declines in basal levels of PRL.

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β2 Mediated inhibition of [3H]dopamine release from nucleus accumbens slices and monoamine levels in a rat model for attention-deficit hyperactivity disorder

Cited by 67 publications

References 33 publications

Dopaminergic System Genes in ADHD Toward a Biological Hypothesis

Dopaminergic System Genes in ADHD Toward a Biological Hypothesis

Neural systems implicated in delayed and probabilistic reinforcement

Infusion of Alpha-2-Adrenergic Agents into the Paraventricular and Arcuate Nuclei of the Hypothalamus in the Siberian Hamster: Opposing Effects on Basal Prolactin

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