Enhanced effect of dopaminergic stimulation on prepulse inhibition in mice deficient in the alpha subunit of Gz

Buuse, Maarten van den; Martin, Sally; Brosda, Jan; Leck, Kwong Joo; Matthaei, Klaus I.; Hendry, Ian A.

doi:10.1007/s00213-005-0181-6

Cited by 26 publications

(15 citation statements)

References 41 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The ability of APO to reduce PPI confirms several previous findings in this mouse strain (Ralph-Williams et al, 2002, 2003; Yee et al, 2004; Russig et al, 2005, van den Buuse et al, 2005; Semenova et al, 2008; Martin et al, 2008; Caldwell et al, 2009) and other strains (Curzon and Decker, 1998; Ukai and Okuda, 2003; Malone et al, 2004; Park et al, 2005; Brea et al, 2006; Depoortère et al, 2007; Yano et al, 2009). While no effect of PRA on PPI was shown in this report, bioactivity was demonstrated by a reduction in startle magnitude at the highest dose tested (10 mg/kg) and by changes in locomotor and exploratory behavior across lower doses.…”

Section: Discussionsupporting

confidence: 90%

The effects of pramipexole on prepulse inhibition and locomotor activity in C57BL/6J mice

Chang¹,

Geyer²,

Buell³

et al. 2010

Behavioural Pharmacology

View full text Add to dashboard Cite

Pramipexole (PRA) is a preferential D3R agonist that in rats and humans modifies prepulse inhibition (PPI) of the acoustic startle reflex, an operational measure of sensorimotor gating. The ability to use similar PPI measures across species, and the relative ease of genetic manipulations in mice, suggests that molecular studies of the D3R regulation of sensorimotor gating might be best pursued in mice. Here, we evaluate the effects of PRA on PPI and locomotion in C57BL/6J mice, the background strain for many gene knockout mouse models. Male C57BL/6J mice were tested for PPI and locomotor activity after injection of PRA. No significant effects of PRA on PPI were seen at any dose (0.1-10.0 mg/kg), but a significant reduction in startle magnitude was observed after 10 mg/kg PRA. In contrast, the D1/2 agonist, apomorphine (5 mg/kg) significantly reduced PPI in these mice. At doses of PRA that did not alter startle magnitude (0.3, 1.0, 3.0 mg/kg), significant decreases in the amount of locomotor and investigatory behavior were observed. Distinct from findings in rats and humans, it appears that either: 1) PRA does not activate D3Rs in C57BL/6J mice, or 2) D3R agonists are not sufficient to alter PPI in this mouse strain.

show abstract

Section: Discussionsupporting

confidence: 90%

The effects of pramipexole on prepulse inhibition and locomotor activity in C57BL/6J mice

Chang¹,

Geyer²,

Buell³

et al. 2010

Behavioural Pharmacology

View full text Add to dashboard Cite

show abstract

“…[ 3 H]YM-09151 binding was conducted at 1 nm in 50 mM Tris-HCl, 120 mM NaCl, 5 mM KCl, 2 mM CaCl 2 , 1 mM MgCl 2 , 0.1 mM pindolol, 0.5 mM DTG (pH 7.4). The displacer was sulpiride at 10 mM (van den Buuse et al, 2005b).…”

Section: [ 3 H] Radioligand Binding and Autoradiographymentioning

confidence: 99%

Clozapine reverses schizophrenia-related behaviours in the metabotropic glutamate receptor 5 knockout mouse: association with N-methyl-d-aspartic acid receptor up-regulation

Gray

Buuse

Scarr

et al. 2008

Int. J. Neuropsychopharm.

116

View full text Add to dashboard Cite

Abnormalities in glutamatergic signalling are proposed in schizophrenia in light of the schizophreniform psychosis elicited by NMDA antagonists. The metabotropic glutamate receptor 5 (mGluR5) interacts closely with the NMDA receptor and is implicated in several behavioural endophenotypes of schizophrenia. We have demonstrated that mice lacking mGluR5 have increased sensitivity to the hyperlocomotive effects of the NMDA antagonist MK-801. Mice lacking mGluR5 also show abnormal locomotor patterns, reduced prepulse inhibition (PPI), and deficits on performance of a short-term spatial memory task on the Y-maze. Chronic administration of the antipsychotic drug clozapine ameliorated the locomotor disruption and reversed the PPI deficit, but did not improve Y-maze performance. Chronic clozapine increased NMDA receptor binding ([3H]MK-801) but did not alter dopamine D2 ([3H]YM-09151), 5-HT2A ([3H]ketanserin), or muscarinic M1/M4 receptor ([3H]pirenzepine), binding in these mice. These results demonstrate behavioural abnormalities that are relevant to schizophrenia in the mGluR5 knockout mouse and a reversal of behaviours with clozapine treatment. These results highlight both the interactions between mGluR5 and NMDA receptors in the determination of schizophreniform behaviours and the potential for the effects of clozapine to be mediated by NMDA receptor regulation.

show abstract

“…Thus far, the phenotypes associated with G␣ z deletion are moderate consequences on platelet function (16,17) and altered behavioral and central nervous system responses to serotonin, morphine, apomorphine, amphetamine, and dopamine agonists (17)(18)(19)(20); the effect of G␣ z knock-out on insulin secretion and glucose homeostasis in these mice has not been determined. We show here that G␣ z -null mice have increased insulin secretion after glucose challenge and a corresponding decrease in blood glucose levels.…”

mentioning

confidence: 99%

Gαz Negatively Regulates Insulin Secretion and Glucose Clearance

Kimple

Joseph

Bailey

et al. 2008

Journal of Biological Chemistry

View full text Add to dashboard Cite

Relatively little is known about the in vivo functions of the ␣ subunit of the heterotrimeric G protein G z (G␣ z ). Clues to one potential function recently emerged with the finding that activation of G␣ z inhibits glucose-stimulated insulin secretion in an insulinoma cell line (Kimple, M. E., Nixon, A. B., Kelly, P., Bailey, C. L., Young, K. H., Fields, T. A., and Casey, P. J. (2005) J. Biol. Chem. 280, 31708 -31713). To extend this study in vivo, a G␣ z knock-out mouse model was utilized to determine whether G␣ z function plays a role in the inhibition of insulin secretion. No differences were discovered in the gross morphology of the pancreatic islets or in the islet DNA, protein, or insulin content between G␣ z -null and wild-type mice. There was also no difference between the insulin sensitivity of G␣ z -null mice and wildtype controls, as measured by insulin tolerance tests. G␣ z -null mice did, however, display increased plasma insulin concentrations and a corresponding increase in glucose clearance following intraperitoneal and oral glucose challenge as compared with wild-type controls. The increased plasma insulin observed in G␣ z -null mice is most likely a direct result of enhanced insulin secretion, since pancreatic islets isolated from G␣ z -null mice exhibited significantly higher glucose-stimulated insulin secretion than those of wild-type mice. Finally, the increased insulin secretion observed in G␣ z -null islets appears to be due to the relief of a tonic inhibition of adenylyl cyclase, as cAMP production was significantly increased in G␣ z -null islets in the absence of exogenous stimulation. These findings indicate that G␣ z may be a potential new target for therapeutics aimed at ameliorating ␤-cell dysfunction in Type 2 diabetes.Insulin secretion from the ␤-cells of the pancreas follows a biphasic pattern, in which an initial peak minutes after stimulation by glucose is followed by a lower magnitude sustained phase over the duration of glucose stimulation. This phenomenon is thought to be due to the interaction of two signaling pathways: the triggering pathway and the amplifying pathway (1, 2). In the initial (triggering) phase of insulin secretion, metabolism of glucose in the mitochondria leads to an increase in cytosolic ATP/ADP ratio, which causes the closure of the ATP-sensitive K ϩ channel (K ATP channel) 2 and membrane depolarization. The resulting membrane depolarization opens voltage-dependent calcium channels, allowing an influx of extracellular Ca 2ϩ and stimulation of calcium-induced calcium release from the endoplasmic reticulum. These intracellular changes lead to exocytosis of a readily releasable pool of insulin granules, a process that involves ATP-dependent insulin granule priming, granule fusion, and insulin release. The amplifying pathway of insulin secretion is also dependent on glucose but does not elevate the intracellular Ca 2ϩ concentrations and is therefore referred to as the K ATP channel-independent pathway (3); the mechanisms underlying this pathway are not as we...

show abstract

Enhanced effect of dopaminergic stimulation on prepulse inhibition in mice deficient in the alpha subunit of Gz

Cited by 26 publications

References 41 publications

The effects of pramipexole on prepulse inhibition and locomotor activity in C57BL/6J mice

The effects of pramipexole on prepulse inhibition and locomotor activity in C57BL/6J mice

Clozapine reverses schizophrenia-related behaviours in the metabotropic glutamate receptor 5 knockout mouse: association with N-methyl-d-aspartic acid receptor up-regulation

Gαz Negatively Regulates Insulin Secretion and Glucose Clearance

Contact Info

Product

Resources

About