Intrastriatal dopamine D1 receptor agonist‐mediated motor behavior is reduced by local neurokinin 1 receptor antagonism

Krolewski, David M.; Bishop, Christopher; Walker, Paul D.

doi:10.1002/syn.20148

Cited by 12 publications

(11 citation statements)

References 54 publications

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“…Further, although antagonism of NK1R within the striatum has no effect on substance P mRNA expression or spontaneous locomotor activity, it prevents a d -amphetamine-induced increase in both these measures (Gonzales-Nicolini and McGinty, 2002). NK1R antagonism in the striatum also prevents hyperactivity mediated by the activation of dopamine D1 receptors (Krolewski, et al ., 2005). Against this background, we reasoned that basal dopamine efflux in the striatum would be unaffected by functional ablation of the NK1R gene, or NK1R antagonism, but that the dopamine response to d -amphetamine would be diminished.…”

Section: Discussionmentioning

confidence: 99%

“…Since cholinergic (M1) receptor knock-out mice are hyperactive (Gerber, et al ., 2001), one explanation for the hyperactivity of NK1R−/− mice could be that their lack of functional NK1R impairs acetylcholine release mediated by D1 receptor activation (Anderson, et al ., 1994). However, this is unlikely because basal dopamine efflux did not differ in the two genotypes and local activation of DRD1-like receptors induces hyperactivity, rather than reduces it (Krolewski, et al ., 2005). An alternative explanation focuses on glutamatergic afferents from the cortex and thalamus, which converge on the cholinergic interneurones and medium-spiny output neurones.…”

Section: Discussionmentioning

confidence: 99%

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NK₁ (TACR₁) receptor gene ‘knockout’ mouse phenotype predicts genetic association with ADHD

et al. 2009

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Mice with functional genetic ablation of the Tacr1 (substance P-preferring receptor) gene (NK1R−/−) are hyperactive. Here, we investigated whether this is mimicked by NK1R antagonism and whether dopaminergic transmission is disrupted in brain regions that govern motor performance. The locomotor activity of NK1R−/− and wild-type mice was compared after treatment with an NK1R antagonist and/or psychostimulant (d-amphetamine or methylphenidate). The inactivation of NK1R (by gene mutation or receptor antagonism) induced hyperactivity in mice, which was prevented by both psychostimulants. Using in vivo microdialysis, we then compared the regulation of extracellular dopamine in the prefrontal cortex (PFC) and striatum in the two genotypes. A lack of functional NK1R reduced (>50%) spontaneous dopamine efflux in the prefrontal cortex and abolished the striatal dopamine response to d-amphetamine. These behavioural and neurochemical abnormalities in NK1R−/− mice, together with their atypical response to psychostimulants, echo attention deficit hyperactivity disorder (ADHD) in humans. These findings prompted genetic studies on the TACR1 gene (the human equivalent of NK1R) in ADHD patients in a case-control study of 450 ADHD patients and 600 screened supernormal controls. Four single-nucleotide polymorphisms (rs3771829, rs3771833, rs3771856, and rs1701137) at the TACR1 gene, previously known to be associated with bipolar disorder or alcoholism, were strongly associated with ADHD. In conclusion, our proposal that NK1R−/− mice offer a mouse model of ADHD was borne out by our human studies, which suggest that DNA sequence changes in and around the TACR1 gene increase susceptibility to this disorder.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

NK₁ (TACR₁) receptor gene ‘knockout’ mouse phenotype predicts genetic association with ADHD

et al. 2009

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“…In most cases, infusing nonselective and selective DA agonists into the caudate-putamen (CPu) affects preweanling and adult rats in a generally similar manner. For example, microinjecting a selective D1 agonist into the CPu increases the locomotor activity of preweanling and adult rats (Kreipke and Walker, 2004; Krolewski et al, 2005; Charntikov et al, 2011). Both age groups also show an intensification of stereotypy when a D1 or D2 agonist is infused into the CPu (Bordi and Meller, 1989; Canales and Iversen, 1998; Waszczak et al, 2002; Kreipke and Walker, 2004; Krolewski et al, 2005; Charntikov et al, 2011).…”

Section: Introductionmentioning

confidence: 99%

“…For example, microinjecting a selective D1 agonist into the CPu increases the locomotor activity of preweanling and adult rats (Kreipke and Walker, 2004; Krolewski et al, 2005; Charntikov et al, 2011). Both age groups also show an intensification of stereotypy when a D1 or D2 agonist is infused into the CPu (Bordi and Meller, 1989; Canales and Iversen, 1998; Waszczak et al, 2002; Kreipke and Walker, 2004; Krolewski et al, 2005; Charntikov et al, 2011). Some interesting age-dependent differences are apparent, however, because selectively stimulating D2 receptors in the dorsal CPu triggers a pronounced locomotor response in preweanling rats (Charntikov et al, 2011), while causing either a reduction (Bordi and Meller, 1989; Canales and Iversen, 1998) or a subtle, biphasic increase in the locomotor activity of adult rats (Van Hartesveldt et al, 1992).…”

Section: Introductionmentioning

confidence: 99%

Dopamine receptor inactivation in the caudate-putamen differentially affects the behavior of preweanling and adult rats

et al. 2012

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The irreversible receptor antagonist N-ethoxycarbonyl-2-ethoxy-1,2-dihydroquinoline (EEDQ) has been used to study the ontogeny of dopamine (DA) receptor functioning in the young and adult rat. Most notably, systemic administration of EEDQ blocks the DA agonist-induced behaviors of adult rats, while leaving the behavior of preweanling rats unaffected. The purpose of the present study was to: (a) determine whether the age-dependent actions of EEDQ involve receptors located in the dorsal caudate-putamen (CPu) and (b) confirm that EEDQ's behavioral effects result from the inactivation of DA receptors rather than some other receptor type. In Experiment 1, EEDQ or DMSO were bilaterally infused into the CPu on PD 17 or PD 84. After 24 h, rats were given bilateral microinjections of the full DA agonist R(–)-propylnorapomorphine (NPA) or vehicle into the dorsal CPu and behavior was assessed for 40 min. In Experiment 2, preweanling rats were treated as just described, except that DA receptors were protected from EEDQ-induced alkylation by administering systemic injections of D1 (SCH23390) and D2 (sulpiride) receptor antagonists. As predicted, microinjecting EEDQ into the dorsal CPu attenuated the NPA-induced locomotor activity and stereotypy of adult rats. In contrast, rats given bilateral EEDQ infusions on PD 17 exhibited a potentiated locomotor response when treated with NPA. Experiment 2 showed that DA receptor inactivation was responsible for NPA's actions. A likely explanation for these results is that EEDQ inactivates a sizable percentage of DA receptors on PD 17, but leaves the remaining receptors in a supersensitive state. This receptor supersensitivity, which probably involves alterations in G protein coupling, could account for NPA-induced locomotor potentiation. Either adult rats do not show a similar EEDQ-induced change in receptor dynamics or DA receptor inactivation was more complete in older animals and effectively eliminated the expression of DA agonist-induced behaviors.

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“…Substance P has been found to contribute to the rewarding effects of opiates (Ripley et al ., 2002; Gadd et al ., 2003). Moreover, antagonists of the substance P receptor display anti-depressant activity (Kramer et al ., 1998; Rupniak et al ., 2001), and modulation of behavior induced by activation of the striatal dopamine D1 receptor (Krolewski et al ., 2005). Recently, we postulated that increased signaling by substance P through the neurokinin-1 receptor of the striatum constitutes one mechanism contributing to the METH-induced toxicity of the dopamine terminals (Yu et al ., 2002, 2004).…”

Section: Discussionmentioning

confidence: 99%

The neurokinin‐1 receptor modulates the methamphetamine‐induced striatal apoptosis and nitric oxide formation in mice

Zhu

Wang

et al. 2009

Journal of Neurochemistry

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,Met (O 2 ) 11 ] substance P; SST, somatostatin; TUNEL, terminal deoxyncleotidyl transferase-mediated dUTP nick end labeling. AbstractIn a previous study we showed that pharmacological blockade of the neurokinin-1 receptors attenuated the methamphetamine (METH)-induced toxicity of the striatal dopamine terminals. In the present study we examined the role of the neurokinin-1 receptors on the METH-induced apoptosis of some striatal neurons. To that end, we administered a single injection of METH (30 mg/kg, i.p.) to male mice. METH induced the apoptosis (terminal deoxyncleotidyl transferasemediated dUTP nick end labeling) of approximately 20% of striatal neurons. This percentage of METH-induced apoptosis was significantly attenuated by either a single injection of the neurokinin-1 receptor antagonist, 17-b-hydroxy-17-a-ethynyl-5-a-androstano [3,2-b]pyrimido[1,2-a]benzimidazole (WIN-51,708) (5 mg/kg, i.p.), or the ablation of the striatal interneurons expressing the neurokinin-1 receptors (cholinergic and somatostatin) with the selective neurotoxin [Sar 9 ,Met (O 2 ) 11 ] substance P-saporin. Next we assessed the levels of striatal 3-nitrotyrosine (3-NT) by HPLC and immunohistochemistry. METH increased the levels of striatal 3-NT and this increase was attenuated by pre-treatment with WIN-51,708. Our data support the hypothesis that METH-induced striatal apoptosis occurs via a mechanism involving the neurokinin-1 receptors and the activation of nitric oxide synthesis. (Freese et al. 2002). Despite a wealth of information on the damaging effects of METH both in laboratory animal species and humans, the mechanism by which METH induces neural damage in the brain remains poorly understood. Treatment with METH augments the release of glutamate in the striatum (Nash and Yamamoto 1992) inducing neurotoxicity in this brain region (Sonsalla et al. 1991). For example, the N-methyl-D-aspartic acid (NMDA) receptor antagonist MK-801 decreases METH-induced striatal dopamine overflow, attenuating damage to the dopamine terminals (O'Dell et al. 1992). Moreover, agents that abrogate the increase in extracellular glutamate also prevent METHinduced decreases in dopamine content (Stephans and Yamamoto 1994). Compelling evidence suggests oxidative stress to be attributable to METH-induced neurodegeneration (De Vito and Wagner 1989). METH-induced dopaminergic neurotoxicity in the striatum depends on the extracellular accumulation of dopamine (O'Dell et al. 1993) and its autooxidation (Fridovich 1986). Pharmacological inhibition of nitric oxide synthase (NOS) and the deletion of the gene for this enzyme in mice protects the striatum from METH suggesting a role for nitric oxide (Itzhak and Ali 1996;Imam et al. 2001a, Imam et al. 2001b.The neuropeptide substance P participates in neurodegeneration. For example, the release of substance P induces glutamate release in the hippocampus of the rodent brain (Liu et al. 1999a). Exposure to the excitotoxin kainate in wild-type mice results in the death of neurons in the hippocampus, but mice...

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Intrastriatal dopamine D1 receptor agonist‐mediated motor behavior is reduced by local neurokinin 1 receptor antagonism

Cited by 12 publications

References 54 publications

NK₁ (TACR₁) receptor gene ‘knockout’ mouse phenotype predicts genetic association with ADHD

NK₁ (TACR₁) receptor gene ‘knockout’ mouse phenotype predicts genetic association with ADHD

Dopamine receptor inactivation in the caudate-putamen differentially affects the behavior of preweanling and adult rats

The neurokinin‐1 receptor modulates the methamphetamine‐induced striatal apoptosis and nitric oxide formation in mice

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Intrastriatal dopamine D1 receptor agonist‐mediated motor behavior is reduced by local neurokinin 1 receptor antagonism

Cited by 12 publications

References 54 publications

NK1 (TACR1) receptor gene ‘knockout’ mouse phenotype predicts genetic association with ADHD

NK1 (TACR1) receptor gene ‘knockout’ mouse phenotype predicts genetic association with ADHD

Dopamine receptor inactivation in the caudate-putamen differentially affects the behavior of preweanling and adult rats

The neurokinin‐1 receptor modulates the methamphetamine‐induced striatal apoptosis and nitric oxide formation in mice

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NK₁ (TACR₁) receptor gene ‘knockout’ mouse phenotype predicts genetic association with ADHD

NK₁ (TACR₁) receptor gene ‘knockout’ mouse phenotype predicts genetic association with ADHD