Drug-induced potentiation of prepulse inhibition of acoustic startle reflex in mice: a model for detecting antipsychotic activity?

Ouagazzal, Abdel‐Mouttalib; Jenck, F.; Moreau, Jean‐Luc

doi:10.1007/s002130100763

Cited by 122 publications

(120 citation statements)

References 1 publication

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“…There are several lines of evidence supporting the independence of drug effect on PPI and startle reflex. For instance, diazepam significantly reduced startle responses in BALB/cByJ and 129/SvEv without affecting PPI, although it affected PPI and startle response simultaneously in C57 mice (Ouagazzal et al, 2001). A study investigating basal acoustic startle response and PPI among several inbred mouse strains showed there was no correlation between the magnitude of basal acoustic startle responses and PPI (Paylor and Crawley, 1997), suggesting differently genetically defined physiological processes are involved in basal acoustic startle and PPI of startle reflex.…”

Section: Discussionmentioning

confidence: 99%

Effect of Dopamine D3 Antagonists on PPI in DBA/2J Mice or PPI Deficit Induced by Neonatal Ventral Hippocampal Lesions in Rats

Zhang

Ballard

Kohlhaas

et al. 2005

Neuropsychopharmacol

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Schizophrenic patients typically exhibit impairment of sensorimotor gating, which can be modeled in animal models such as the test of prepulse inhibition of startle response (PPI) in rodents. It has been found that antipsychotics enhanced PPI in DBA mice and reversed the PPI deficit induced by neonatal ventral hippocampal (NVH) lesions in rats. However, the relative involvement of D 3 and D 2 receptors in these effects is unknown since all antipsychotics are D 2 /D 3 antagonists with limited binding preference at D 2 receptors. Therefore, in the current study, we investigated the influence of several dopamine antagonists with higher selectivity at D 3 vs D 2 receptors on PPI in DBA/ 2J mice and in NVH-lesioned rats. The PPI in DBA/2J mice was enhanced by the nonselective D 2 /D 3 antagonists, haloperidol at 0.3-3 mg/ kg, or risperidone at 0.3-1 mg/kg, while PPI-enhancing effects were observed after the administration of higher doses of the preferential D 3 /D 2 antagonist, BP 897 at 8 mg/kg, and the selective D 3 antagonists, SB 277011 at 30 mg/kg and A-437203 at 30 mg/kg. No effect was observed following the treatment with the selective D 3 antagonist, AVE 5997 up to 30 mg/kg. The PPI deficits induced by NVH lesions were reversed by haloperidol but not by the more selective D 3 antagonists, A-437203 and AVE 5997. BP 897 enhanced PPI nonselectivity, that is, in both lesioned and nonlesioned rats. In summary, the present study indicates that PPI-enhancing effects induced by antipsychotics in DBA/2J mice and in NVH-lesioned rats are unlikely to be mediated by D 3 receptors.

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Section: Discussionmentioning

confidence: 99%

Effect of Dopamine D3 Antagonists on PPI in DBA/2J Mice or PPI Deficit Induced by Neonatal Ventral Hippocampal Lesions in Rats

Zhang

Ballard

Kohlhaas

et al. 2005

Neuropsychopharmacol

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“…Haloperidol (Serenace, Searle Laboratories, Crows Nest, NSW, Australia) and clozapine (Sigma Chemical Co., St Louis, MO, USA) were administered at concentrations of 1 and 5 mg/kg. 40 Treatments were randomized and mice (n = 10-12 per group) were allowed to recover from the drug treatment for a minimum of 7 days in between treatments, each mouse undergoing behavioral testing under the influence of clozapine 1 and 5 mg/kg, haloperidol 1 and 5 mg/kg and saline. The 1 mg/kg doses of each drug had no statistically significant effects and thus only 5 mg/kg data are presented here.…”

Section: Drug Treatmentmentioning

confidence: 99%

Phospholipase C-β1 knockout mice exhibit endophenotypes modeling schizophrenia which are rescued by environmental enrichment and clozapine administration

et al. 2007

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Phospholipase C-b1 (PLC-b1) is a rate-limiting enzyme implicated in postnatal-cortical development and neuronal plasticity. PLC-b1 transduces intracellular signals from specific muscarinic, glutamate and serotonin receptors, all of which have been implicated in the pathogenesis of schizophrenia. Here, we present data to show that PLC-b1 knockout mice display locomotor hyperactivity, sensorimotor gating deficits as well as cognitive impairment. These changes in behavior are regarded as endophenotypes homologous to schizophrenialike symptoms in rodents. Importantly, the locomotor hyperactivity and sensorimotor gating deficits in PLC-b1 knockout mice are subject to beneficial modulation by environmental enrichment. Furthermore, clozapine but not haloperidol (atypical and typical antipsychotics, respectively) rescues the sensorimotor gating deficit in these animals, suggesting selective predictive validity. We also demonstrate a relationship between the beneficial effects of environmental enrichment and levels of M1/M4 muscarinic acetylcholine receptor binding in the neocortex and hippocampus. Thus we have demonstrated a novel mouse model, displaying disruption of multiple postsynaptic signals implicated in the pathogenesis of schizophrenia, a relevant behavioral phenotype and associated gene-environment interactions.

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“…injection of vehicle or drug. Based on previous reports (Ouagazzal et al, 2001;RalphWilliams et al, 2002), animals in the amphetamine experiment were placed immediately into the startle chambers, animals in the haloperidol experiments remained in the holding cages for an additional 30 min, and animals in the rolipram experiments remained in the holding cages for an additional 15 min, to allow for differences in drug kinetics. After the testing session ended, animals were promptly returned to their home cage.…”

Section: Ppimentioning

confidence: 99%

“…Amphetamine, an indirect dopaminergic agonist, decreases PPI via dopamine D2 receptors (Ralph-Williams et al, 2002) that inhibit AC activity (Neves et al, 2002). Conversely, haloperidol, a typical antipsychotic that blocks D2 receptors (cf., Miyamoto et al, 2005) and increases cAMP signaling in forebrain structures (Berndt and Schwabe, 1973;Kaneko et al, 1992;Kaplan et al, 1999;Dwivedi et al, 2002; but see Kebabian et al, 1972;Carenzi et al, 1975), increases PPI (Ouagazzal et al, 2001). Thus, there appears to be a relationship between cAMP and PPI levels.…”

Section: Introductionmentioning

confidence: 95%

Constitutive Activation of Gαs within Forebrain Neurons Causes Deficits in Sensorimotor Gating Because of PKA-Dependent Decreases in cAMP

Kelly

Isiegas

Cheung

et al. 2006

Neuropsychopharmacol

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Sensorimotor gating, the ability to automatically filter sensory information, is deficient in a number of psychiatric disorders, yet little is known of the biochemical mechanisms underlying this critical neural process. Previously, we reported that mice expressing a constitutively active isoform of the G-protein subunit Gas (Gas*) within forebrain neurons exhibit decreased gating, as measured by prepulse inhibition of acoustic startle (PPI). Here, to elucidate the biochemistry regulating sensorimotor gating and to identify novel therapeutic targets, we test the hypothesis that Gas* causes PPI deficits via brain region-specific changes in cyclic AMP (cAMP) signaling. As predicted from its ability to stimulate adenylyl cyclase, we find here that Gas* increases cAMP levels in the striatum. Suprisingly, however, Gas* mice exhibit reduced cAMP levels in the cortex and hippocampus because of increased cAMP phosphodiesterase (cPDE) activity. It is this decrease in cAMP that appears to mediate the effect of Gas* on PPI because Rp-cAMPS decreases PPI in C57BL/ 6J mice. Furthermore, the antipsychotic haloperidol increases both PPI and cAMP levels specifically in Gas* mice and the cPDE inhibitor rolipram also rescues PPI deficits of Gas* mice. Finally, to block potentially the pathway that leads to cPDE upregulation in Gas* mice, we coexpressed the R(AB) transgene (a dominant-negative regulatory subunit of protein kinase A (PKA)), which fully rescues the reductions in PPI and cAMP caused by Gas*. We conclude that expression of Gas* within forebrain neurons causes PPI deficits because of a PKAdependent decrease in cAMP and suggest that cAMP PDE inhibitors may exhibit antipsychotic-like therapeutic effects.

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Drug-induced potentiation of prepulse inhibition of acoustic startle reflex in mice: a model for detecting antipsychotic activity?

Cited by 122 publications

References 1 publication

Effect of Dopamine D3 Antagonists on PPI in DBA/2J Mice or PPI Deficit Induced by Neonatal Ventral Hippocampal Lesions in Rats

Effect of Dopamine D3 Antagonists on PPI in DBA/2J Mice or PPI Deficit Induced by Neonatal Ventral Hippocampal Lesions in Rats

Phospholipase C-β1 knockout mice exhibit endophenotypes modeling schizophrenia which are rescued by environmental enrichment and clozapine administration

Constitutive Activation of Gαs within Forebrain Neurons Causes Deficits in Sensorimotor Gating Because of PKA-Dependent Decreases in cAMP

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