The dopamine D3 receptor antagonist NGB 2904 increases spontaneous and amphetamine-stimulated locomotion

Pritchard, Laurel M.; Newman, Amy Hauck; McNamara, Robert K.; Logue, Aaron D; Taylor, Benjamin; Welge, Jeffrey A.; Xu, Ming; Zhang, Jianhua; Richtand, Neil M.

doi:10.1016/j.pbb.2007.02.019

Cited by 43 publications

(34 citation statements)

References 60 publications

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“…The dose of NGB2904 pretreatment used is in accordance with previous studies in which NGB2904 enhanced cocaine-induced increases in NAc dopamine concentration and increased amphetaminestimulated locomotion [32,35,36] . In addition, we performed a dose-effect experiment by administering different dosages of NGB2904 (0.1, 0.5, 1, 3, and 5 mg/kg i.p.)…”

Section: Drug Treatmentsupporting

confidence: 60%

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Signaling via Dopamine D1 and D3 Receptors Oppositely Regulates Cocaine-Induced Structural Remodeling of Dendrites and Spines

Zhang

Li²,

Liu³

et al. 2011

Neurosignals

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Repeated exposure to cocaine can induce persistent alterations in the brain. The structural remodeling of dendrites and dendritic spines is thought to play a critical role in cocaine addiction. We previously demonstrated that signaling via dopamine D1 and D3 receptors have opposite effects on cocaine-induced gene expression. Here, we show that cocaine-induced structural remodeling in the nucleus accumbens (NAc) and caudoputamen (CPu) is mediated by D1 receptors and inhibited by D3 receptors. In addition, chronic exposure to cocaine results in an altered number of asymmetric spine synapses via the actions of both D1 and D3 receptors. The contradictory effects of D1 and D3 receptor signaling on cocaine-induced structural remodeling is associated with NMDA-receptor R1 subunit (NR1) phosphorylation, and is dependent upon the activation of extracellular signal-regulated kinase (ERK). In addition, we found that D1 and D3 receptor signaling has contradictory effects upon the activation of the myocyte enhancer factor 2 (MEF2), which is involved in the dendritic remodeling after cocaine treatment. Together, these data suggest that dopamine D1 and D3 receptors differentially regulate the cocaine-induced structural remodeling of dendrites and spines via mechanisms involving the consecutive actions of NR1 phosphorylation, ERK activation, and MEF2 activity in the NAc and CPu.

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Section: Drug Treatmentsupporting

confidence: 60%

“…A number of in vivo studies further support the selectivity of NGB2904 for D3 receptors [32,35,36] . To confirm the selectivity of NGB2904 in our experiments, we conducted a dose-response experiment by treating mice with different dosages of NGB2904 (0.1, 0.5, 1, 3, and 5 mg/kg, i.p.)…”

Section: Cocaine-induced Structural Remodeling Of Dendrites and Spinementioning

confidence: 87%

Signaling via Dopamine D1 and D3 Receptors Oppositely Regulates Cocaine-Induced Structural Remodeling of Dendrites and Spines

Zhang

Li²,

Liu³

et al. 2011

Neurosignals

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“…Preclinical data suggest that activation of the dopamine D 3 receptor with low doses of agonists, such as 7-OH-DPAT, quinelorane and PD 128,907, inhibits spontaneous motor activity (Daly & Waddington, 1993 ;Millan et al 2004), probably by activation of receptors in the NAc (Ouagazzal & Creese, 2000). By contrast, D 3 antagonists, such as nafadotride, U99194A, and NGB 2904, enhance locomotor activity (Clifford & Waddington, 1998 ;Pritchard et al 2007 ;Sautel et al 1995) in the rodent but are without effect in D 3 receptor knockout mice (Pritchard et al 2007). Although such findings were initially controversial due to the lack of selectivity of the original compounds used (Boulay et al 1999), more selective antagonists, like S33084, have confirmed that blockade of the D 3 receptor does not reduce spontaneous locomotor activity in an open field (Millan et al 2004), consistent with the current data : moreover, it produces a mild antiparkinsonian effect in the MPTP-lesioned marmoset without producing dyskinesia (Silverdale et al 2004).…”

Section: Discussionmentioning

confidence: 99%

Blockade of dopamine D3 but not D2 receptors reverses the novel object discrimination impairment produced by post-weaning social isolation: implications for schizophrenia and its treatment

Watson

Marsden

Millan

et al. 2011

Int. J. Neuropsychopharm.

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Dopamine D₃ receptors are densely expressed in mesolimbic projection areas, and selective antagonists enhance cognition, consistent with their potential therapeutic use in the treatment of schizophrenia. This study examines the effect of dopamine D₃ vs. D₂ receptor antagonists on the cognitive impairment and hyperactivity produced by social isolation of rat pups, in a neurodevelopmental model of certain deficits of schizophrenia. Three separate groups of male Lister hooded rats were group-housed or isolation-reared from weaning. Six weeks later rats received either vehicle or the dopamine D₃ selective antagonist, S33084 (0.04 and 0.16 mg/kg), the preferential D₃ antagonist, S33138 (0.16 and 0.63 mg/kg) or the preferential D₂ antagonist, L-741,626 (0.63 mg/kg) s.c. 30 min prior to recording; horizontal locomotor activity in a novel arena for 60 min and, the following day, novel object discrimination using a 2-h inter-trial interval. Isolation rearing induced locomotor hyperactivity in a novel arena and impaired novel object discrimination compared to that in group-housed littermates. Both S33084 and S33138 restored novel object discrimination deficits in isolation-reared rats without affecting discrimination in group-housed controls. By contrast, L-741,626 impaired novel object discrimination in group-housed rats, without affecting impairment in isolates. S33084 (0.16 mg/kg), S33138 and, less markedly, L741,626 reduced the locomotor hyperactivity in isolates without attenuating activity in group-housed controls. Selective blockade of dopamine D₃ receptors reverses the visual recognition memory deficit and hyperactivity produced by isolation rearing. These data support further investigation of the potential use of dopamine D₃ receptor antagonists to treat schizophrenia.

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“…Finally, we observed an increase, although not significant, in active and inactive lever pressing in rats administered with the lower dose of NGB 2904 (0.1 mg/kg), under FD condition. Although speculating on a non-significant effect is of questionable value, it is interesting to note that a stimulatory effect of low doses of NGB 2904 has been demonstrated on spontaneous and amphetamine-induced locomotor activity in mice (Pritchard et al, 2007).…”

Section: Discussionmentioning

confidence: 99%

A role for dopamine D1-like receptors in acute food deprivation-induced reinstatement of heroin seeking in rats

Tobin

Newman

Quinn

et al. 2008

Int. J. Neuropsychopharm.

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Dopamine has a critical role in drug reinforcement and the reinstatement of drug seeking due to priming or exposure to drug-associated cues. In contrast, the role of dopamine in stress-induced reinstatement is not clear. We have previously demonstrated that acute food deprivation, a clinically relevant stressor, reinstates heroin seeking in rats via a leptin-dependent mechanism. Recent reports have suggested a modulating role for leptin on dopamine transmission and drug-related behaviours. Thus, here we investigated the role of dopamine in acute food deprivation-induced reinstatement of heroin seeking. Rats were trained to self-administer heroin (0.05 mg/kg per infusion) for 10 d. Following training, heroin seeking was extinguished and rats were tested for 48-h food deprivation-induced reinstatement while pretreated with the dopamine D1-, D2-, or D3-like receptor antagonists: SCH 23390 (0.0, 5.0 or 10.0 microg/kg), raclopride (0.0, 50.0 or 100.0 microg/kg) or NGB 2904 (0.0, 0.1 or 5.0 mg/kg), respectively. The dopamine D1-like receptor antagonist, SCH 23390, but neither of the other antagonists, showed a dose-dependent attenuation of food deprivation-induced reinstatement. Our results suggest that acute food deprivation-induced reinstatement may be mediated, at least in part, by activation of the dopamine D1-like receptor.

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The dopamine D3 receptor antagonist NGB 2904 increases spontaneous and amphetamine-stimulated locomotion

Cited by 43 publications

References 60 publications

Signaling via Dopamine D1 and D3 Receptors Oppositely Regulates Cocaine-Induced Structural Remodeling of Dendrites and Spines

Signaling via Dopamine D1 and D3 Receptors Oppositely Regulates Cocaine-Induced Structural Remodeling of Dendrites and Spines

Blockade of dopamine D3 but not D2 receptors reverses the novel object discrimination impairment produced by post-weaning social isolation: implications for schizophrenia and its treatment

A role for dopamine D1-like receptors in acute food deprivation-induced reinstatement of heroin seeking in rats

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