Accumbal dopamine D2 receptors are important for sensorimotor gating in C3H mice

Mohr, Daniela; Pilz, P.; Plappert, Claudia F.; Fendt, Markus

doi:10.1097/wnr.0b013e3282e9a863

Cited by 9 publications

(7 citation statements)

References 23 publications

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“…5). Quinpirole (0.1 lM) significantly inhibited both the ())nicotine ()42.50 ± 3.75%) and the 4-AP ()57.59 ± 5.18%) [ 3 H]DA overflow in the wild type mice, which confirms the existence of DA autoreceptors also in the mouse NAc (Messier et al 1991;Hitzemann et al 2003;Mizuno et al 2007;Mohr et al 2007). In the b2 knockout mice the ())nicotine evoked [ 3 H]DA overflow did not occur anymore confirming that in mice the majority of the nAChR subtypes which modulate DA accumbal release possesses b2 subunits (Champtiaux et al 2003;Molles et al 2006;Grady et al 2007).…”

Section: Effects Of Quinpirole On [ 3 H]da Release Evoked By 4-ap or supporting

confidence: 61%

Pre‐synaptic nicotinic and D₂ receptors functionally interact on dopaminergic nerve endings of rat and mouse nucleus accumbens

Grilli

Zappettini

Zoli

et al. 2009

Journal of Neurochemistry

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The existence of pre-synaptic auto-and hetero receptors which modulate neurotransmitter release is well documented. Emerging evidence show that in some cases these presynaptic receptors may also cross-talk with each other. The aim of the present work was to investigate whether acetylcholine receptors (nAChRs) and dopamine (DA) autoreceptors, which are both able to modulate DA release, functionally interact on the same nerve endings. We used rat and mouse nucleus accumbens synaptosomes pre-labeled with [ 3 H]DA and exposed to nicotinic and dopaminergic receptor ligands. Both nicotinic agonists and 4-aminopyridine (4-AP) provoked [ 3 H]DA release which was inhibited by quinpirole and blocked by sulpiride and raclopride. Both the inhibitory effect of quinpirole and the stimulatory effect of ())nicotine did not change when the nAChRs or the DA receptors were desensitized. ())Nicotine and 4-AP were able to stimulate [ 3 H]DA overflow also in mouse synaptosomes and this overflow was partially inhibited by quinpirole. In the b 2 knockout mice quinpirole was still able to inhibit the [ 3 H]DA overflow elicited by 4-AP. To conclude: in rat and mouse the ())nicotine evoked-release can be modulated by D 2 /D 3 autoreceptors present on the DA terminals and nAChRs function is independent from D 2 /D 3 autoreceptors which themselves may function independently from the activation of nAChRs.

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Section: Effects Of Quinpirole On [ 3 H]da Release Evoked By 4-ap or supporting

confidence: 61%

Pre‐synaptic nicotinic and D₂ receptors functionally interact on dopaminergic nerve endings of rat and mouse nucleus accumbens

Grilli

Zappettini

Zoli

et al. 2009

Journal of Neurochemistry

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“…Startle and PPI responses to an acoustic startle stimulus can be measured in mice and humans [51][52][53], and decreased PPI is found in patients with schizophrenia [54], as well as in mouse models relevant to schizophrenia [8,55,56]. In Dys single heterozygous (D3 +/+ × Dys +/− ) mice, startle reactivity was increased (Fig.…”

Section: Marginal Effects Of D3-dys Genetic Interactions In Social Behavior Locomotor Activity Startle and Ppi Responsesmentioning

confidence: 99%

The epistatic interaction between the dopamine D3 receptor and dysbindin-1 modulates higher-order cognitive functions in mice and humans

et al. 2019

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The dopamine D2 and D3 receptors are implicated in schizophrenia and its pharmacological treatments. These receptors undergo intracellular trafficking processes that are modulated by dysbindin-1 (Dys). Indeed, Dys variants alter cognitive responses to antipsychotic drugs through D2-mediated mechanisms. However, the mechanism by which Dys might selectively interfere with the D3 receptor subtype is unknown. Here, we revealed an interaction between functional genetic variants altering Dys and D3. Specifically, both in patients with schizophrenia and in genetically modified mice, concomitant reduction in D3 and Dys functionality was associated with improved executive and working memory abilities. This D3/Dys interaction produced a D2/D3 imbalance favoring increased D2 signaling in the prefrontal cortex (PFC) but not in the striatum. No epistatic effects on the clinical positive and negative syndrome scale (PANSS) scores were evident, while only marginal effects on sensorimotor gating, locomotor functions, and social behavior were observed in mice. This genetic interaction between D3 and Dys suggests the D2/D3 imbalance in the PFC as a target for patient stratification and procognitive treatments in schizophrenia.

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“…Geyer et al 2001), but of D1 receptors in mice (Ralph-Williams et al 2003a;Ralph and Caine 2005). Within a restricted set of stimulus parameters (particularly prepulse intervals), infusion of D2 agonists into the nucleus accumbens decreases PPI in rats and increases PPI in mice (Mohr et al 2007). This issue is not yet settled, as mice lacking D2 receptors are insensitive to the PPI-disruptive effects of d-amphetamine (Ralph et al 1999), and some mouse strains exhibit "rat-like" PPI sensitivity to D2 agonists (Ralph and Caine 2007).…”

Section: Treatmentmentioning

confidence: 99%

Realistic expectations of prepulse inhibition in translational models for schizophrenia research

et al. 2008

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Introduction Under specific conditions, a weak lead stimulus, or "prepulse", can inhibit the startling effects of a subsequent intense abrupt stimulus. This startle-inhibiting effect of the prepulse, termed "prepulse inhibition" (PPI), is widely used in translational models to understand the biology of brain based inhibitory mechanisms and their deficiency in neuropsychiatric disorders. In 1981, four published reports with "prepulse inhibition" as an index term were listed on Medline; over the past 5 years, new published Medline reports with "prepulse inhibition" as an index term have appeared at a rate exceeding once every 2.7 days (n=678). Most of these reports focus on the use of PPI in translational models of impaired sensorimotor gating in schizophrenia. This rapid expansion and broad application of PPI as a tool for understanding schizophrenia has, at times, outpaced critical thinking and falsifiable hypotheses about the relative strengths vs. limitations of this measure. Objectives This review enumerates the realistic expectations for PPI in translational models for schizophrenia research, and provides cautionary notes for the future applications of this important research tool. Conclusion In humans, PPI is not "diagnostic"; levels of PPI do not predict clinical course, specific symptoms, or individual medication responses. In preclinical studies, PPI is valuable for evaluating models or model organisms relevant to schizophrenia, "mapping" neural substrates of deficient PPI in schizophrenia, and advancing the discovery and development of novel therapeutics. Across species, PPI is a reliable, robust quantitative phenotype that is useful for probing the neurobiology and genetics of gating deficits in schizophrenia.

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Accumbal dopamine D2 receptors are important for sensorimotor gating in C3H mice

Cited by 9 publications

References 23 publications

Pre‐synaptic nicotinic and D₂ receptors functionally interact on dopaminergic nerve endings of rat and mouse nucleus accumbens

Pre‐synaptic nicotinic and D₂ receptors functionally interact on dopaminergic nerve endings of rat and mouse nucleus accumbens

The epistatic interaction between the dopamine D3 receptor and dysbindin-1 modulates higher-order cognitive functions in mice and humans

Realistic expectations of prepulse inhibition in translational models for schizophrenia research

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Accumbal dopamine D2 receptors are important for sensorimotor gating in C3H mice

Cited by 9 publications

References 23 publications

Pre‐synaptic nicotinic and D2 receptors functionally interact on dopaminergic nerve endings of rat and mouse nucleus accumbens

Pre‐synaptic nicotinic and D2 receptors functionally interact on dopaminergic nerve endings of rat and mouse nucleus accumbens

The epistatic interaction between the dopamine D3 receptor and dysbindin-1 modulates higher-order cognitive functions in mice and humans

Realistic expectations of prepulse inhibition in translational models for schizophrenia research

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Pre‐synaptic nicotinic and D₂ receptors functionally interact on dopaminergic nerve endings of rat and mouse nucleus accumbens

Pre‐synaptic nicotinic and D₂ receptors functionally interact on dopaminergic nerve endings of rat and mouse nucleus accumbens