Dopamine phenotype and behaviour in animal models: in relation to attention deficit hyperactivity disorder

Viggiano, D.; Ruocco, L; Sadile, A.G.

doi:10.1016/j.neubiorev.2003.08.006

Cited by 101 publications

(106 citation statements)

References 170 publications

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“…DAT −/− mice were proposed as an animal model of ADHD (Viggiano et al, 2003) and in this respect our findings of increased basal BGluM levels in TH and CB may suggest that increased BGluM due to persistent elevated DA levels in these brain regions may be a factor contributing to the phenotype associated with ADHD.…”

Section: Dat −/− Mice Have Significantly Greater Baseline Bglum Than mentioning

confidence: 56%

The effects of cocaine on regional brain glucose metabolism is attenuated in dopamine transporter knockout mice

Thanos

Michaelides

Benveniste

et al. 2008

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Cocaine's ability to block the dopamine transporter (DAT) is crucial for its reinforcing effects. However the brain functional consequences of DAT blockade by cocaine are less clear since they are confounded by its concomitant blockade of norepinephrine and serotonin transporters. To separate the dopaminergic from the non-dopaminergic effects of cocaine on brain function we compared the regional brain metabolic responses to cocaine between dopamine transporter deficient (DAT −/− ) mice with that of their DAT +/+ littermates. We measured regional brain metabolism (marker of brain function) with 2-[18F]-fluoro-2-deoxy-D-glucose (FDG) and microPET (μPET) before and after acute cocaine administration (i.p. 10 mg/kg). Scans were conducted 2 weeks apart. At baseline DAT −/− mice had significantly greater metabolism in thalamus and cerebellum than DAT +/+ . Acute cocaine decreased whole brain metabolism and this effect was greater in DAT +/+ (15%) than in DAT −/− mice (5%). DAT +/+ mice showed regional decreases in the olfactory bulb, motor cortex, striatum, hippocampus, thalamus and cerebellum whereas DAT −/− mice showed decreases only in thalamus. The differential pattern of regional responses to cocaine in DAT −/− and DAT +/+ suggests that most of the brain metabolic changes from acute cocaine are due to DAT blockade. Cocaine-induced decreases in metabolism in thalamus (region with dense noradrenergic innervation) in DAT −/− suggest that these were mediated by cocaine's blockade of norepinephrine transporters. The greater baseline metabolism in DAT −/− than DAT +/+ mice in cerebellum (brain region mostly devoid of DAT) suggests that dopamine indirectly regulates activity of these brain regions.

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Section: Dat −/− Mice Have Significantly Greater Baseline Bglum Than mentioning

confidence: 56%

The effects of cocaine on regional brain glucose metabolism is attenuated in dopamine transporter knockout mice

Thanos

Michaelides

Benveniste

et al. 2008

Synapse

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“…HI on the 5-CSRTT has been associated in vitro with increased DA release in the NAcbS (Diergaarde et al, 2008), whereas lower midbrain DA D2/3R availability in highly impulsive humans has also been proposed to be associated with enhanced DA activity (Buckholtz et al, 2010). DA D2R are expressed on GABA neurons within the ventral striatum, and also on VTA DA neurons where they are presynaptic and function as autoreceptors that regulate DA release associated with behavioral activation (Viggiano et al, 2003).…”

Section: Discussionmentioning

confidence: 99%

Cocaine Modulation of Frontostriatal Expression of Zif268, D2, and 5-HT2c Receptors in High and Low Impulsive Rats

Besson

Pelloux

Dilleen

et al. 2013

Neuropsychopharmacol

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Impulsivity shares high comorbidity with substance abuse in humans, and high impulsivity (HI) in rats has been identified as a predictive factor for cocaine addiction-like behavior. Despite the evidence that high impulsivity is associated with altered function of corticostriatal networks, the specific neural substrates underlying the increased vulnerability of impulsive individuals to develop cocaine addiction remain unknown. We therefore investigated specific neural correlates of HI within the corticostriatal circuitry and determined how they interact with a protracted history of cocaine self-administration. We used in situ hybridization to map brain expression of two major genes implicated in impulsivity, encoding the dopamine D2 receptor (DA D2R) and the 5-HT2c receptor (5-HT2cR), and an immediate early gene associated with neuronal plasticity, zif268, in groups of rats selected for HI and low impulsivity (LI) on a 5-choice serial reaction time task (5-CSRTT) immediately after 5-CSRTT training, and following 10 or 50 days of cocaine self-administration. HI rats exhibited decreased DA D2R mRNA in the mesolimbic pathway, and increased 5-HT2cR mRNA in the orbitofrontal cortex compared with LI rats. HI rats also showed decreased zif268 mRNA in the ventral and dorsomedial striatum. Cocaine exposure decreased striatal D2R mRNA in both HI and LI rats, decreased 5-HT2cR mRNA differentially in striatal and prefrontal areas between HI and LI rats, and selectively decreased zif268 mRNA in the orbitofrontal and infralimbic cortices of HI animals. These findings implicate novel markers underlying the vulnerability of impulsive rats to cocaine addiction that localize to the OFC, infralimbic cortex, and striatum.

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“…However, we provide functional evidence that trait-like impulsivity is nonetheless dependent on intra-NAcb DA neurotransmission involving DA D2/3 receptors. As an increasing or decreasing DA neurotransmission enhances or reduces, respectively, impulsivity on the 5-CSRT task (Cole and Robbins, 1989;Pattij and Vanderschuren, 2008), it could be hypothesized that HI rats show increased DA activity as compared with LI animals, as a consequence of too few DA D2/3 receptors in the NAcb (Dalley et al, 2007) functioning as autoreceptors (Viggiano et al, 2003). Indeed, impulsivity on the 5-CSRT task has been associated in vitro with high and low DA release in the NAcbS and NAcbC, respectively (Diergaarde et al, 2008).…”

Section: Dopamine Receptor Modulation Of Impulsivity M Besson Et Almentioning

confidence: 99%

Dissociable Control of Impulsivity in Rats by Dopamine D2/3 Receptors in the Core and Shell Subregions of the Nucleus Accumbens

Besson

Belin

McNamara

et al. 2009

Neuropsychopharmacol

121

111

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Previous research has identified the nucleus accumbens (NAcb) as an important brain region underlying inter-individual variation in impulsive behavior. Such variation has been linked to decreased dopamine (DA) D2/3 receptor availability in the ventral striatum of rats exhibiting spontaneously high levels of impulsivity on a 5-choice serial reaction time (5-CSRT) test of sustained visual attention. This study investigated the involvement of DA D2/3 receptors in the NAcb core (NAcbC) and the NAcb shell (NAcbS) in impulsivity. We investigated the effects of a DA D2/3 receptor antagonist (nafadotride) and a DA D2/3 partial agonist (aripiprazole) infused directly into either the NAcbC or NAcbS of rats selected for high (HI) and low (LI) impulsivity on the 5-CSRT task. Nafadotride increased significantly the level of impulsivity when infused into the NAcbS, but decreased impulsivity when infused into the NAcbC of HI rats. By contrast, intraNAcb microinfusions of aripiprazole did not affect impulsivity. Systemic administration of nafadotride had no effect on impulsive behavior but increased the number of omissions and correct response latencies, whereas systemic injections of aripiprazole decreased impulsive and perseverative behavior, and increased the number of omissions and correct response latencies. These findings indicate an opponent modulation of impulsive behavior by DA D2/3 receptors in the NAcbS and NAcbC. Such divergent roles may have relevance for the etiology and treatment of clinical disorders of behavioral control, including attention-deficit hyperactivity disorder and drug addiction.

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Dopamine phenotype and behaviour in animal models: in relation to attention deficit hyperactivity disorder

Cited by 101 publications

References 170 publications

The effects of cocaine on regional brain glucose metabolism is attenuated in dopamine transporter knockout mice

The effects of cocaine on regional brain glucose metabolism is attenuated in dopamine transporter knockout mice

Cocaine Modulation of Frontostriatal Expression of Zif268, D2, and 5-HT2c Receptors in High and Low Impulsive Rats

Dissociable Control of Impulsivity in Rats by Dopamine D2/3 Receptors in the Core and Shell Subregions of the Nucleus Accumbens

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