The atypical antipsychotic, remoxipride, blocks phencyclidine-induced disruption of prepulse inhibition in the rat

Johansson, Christina; Jackson, David M.; Svensson, Lennart

doi:10.1007/bf02247475

Cited by 77 publications

(60 citation statements)

References 27 publications

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“…This dissociation between startle and prepulse inhibition has been reported previously in studies using rats (e.g. Mansbach et al 1988;Bakshi et al 1994;Johansson et al 1994Johansson et al , 1995. The current findings support the previous research and indicate that startle and prepulse inhibition are likely to be under different genetic control.…”

Section: Discussionsupporting

confidence: 92%

Inbred strain differences in prepulse inhibition of the mouse startle response

Paylor¹,

Crawley²

1997

Psychopharmacology

357

250

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Prepulse inhibition is the phenomenon in which a weak prepulse stimulus suppresses the response to a startling stimulus. Patients with schizophrenia have impaired prepulse inhibition which is thought to reflect dysfunctional sensorimotor gating mechanisms. To investigate the potential genetic basis for differences in sensorimotor gating, the responses of 13 inbred strains of mice were evaluated using the prepulse inhibition paradigm. Ten male mice from A/J, AKR/J, BALB/cByJ, BUB/BnJ, C3H/HeJ, C57BL/6J, C57BL/10J, DBA/2J, FVB/NJ, ST/bJ, 129/J, 129/SvJ, 129/SvEvTac inbred strains were tested for acoustic prepulse inhibition of acoustic and tactile startle responses. There was a wide range of responses among the inbred strains of mice. Exact strain distributions were determined for each combination of prepulse sound level and startle stimulus. In general, mice from the 129/SvEvTac, AKR/J, 129/J, and 129/SvJ strains displayed high levels of prepulse inhibition of both the acoustic and tactile startle responses. C57BL/6J, C57BL/10J and BUB/BnJ mice showed low levels of prepulse inhibition. There was also a wide range in the amplitude of the acoustic and tactile startle responses. C57BL/10J and FVB/NJ mice displayed the greatest startle responses and DBA/2J, 129/J and 129/SvJ had the poorest startle responses. There was no correlation between the level of prepulse inhibition and the amplitude of the startle response. These findings indicate that inbred strains of mice may be a useful tool to study the genetic basis of sensorimotor gating.

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Section: Discussionsupporting

confidence: 92%

Inbred strain differences in prepulse inhibition of the mouse startle response

Paylor¹,

Crawley²

1997

Psychopharmacology

357

250

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“…The predictive model was expanded significantly by the observation that putative APs with novel chemical properties were distinguished by their ability to block the PPI-disruptive effects of NMDA antagonists (Johansson et al 1994;Bakshi et al 1994). Indeed, the prevailing wisdom of the early 1990s was that the ability to prevent the PPI-disruptive effects of NMDA antagonists such as phencyclidine and ketamine might predict the properties unique to "atypical" or second-generation APs (SGAPs) and thereby identify agents that would be both more clinically effective and better tolerated than first-generation APs.…”

Section: The Evolution Of Prepulse Inhibition As a Validated Animal Mmentioning

confidence: 99%

Animal Models of Deficient Sensorimotor Gating in Schizophrenia: Are They Still Relevant?

Swerdlow

Light

2015

Translational Neuropsychopharmacology

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Animal models of impaired sensorimotor gating, as assessed by prepulse inhibition (PPI) of startle, have demonstrated clear validity at face, predictive, and construct levels for schizophrenia (SZ) therapeutics, neurophysiological endophenotypes, and potential causative insults for this group of disorders. However, with the growing recognition of the heterogeneity of the schizophrenias, and the less sanguine view of the clinical value of antipsychotic (AP) medications, our field must look beyond "validity," to assess the actual utility of these models. At a substantial cost in terms of research support and intellectual capital, what has come from these models, that we can say has actually helped schizophrenia patients? Such introspection is timely, as we are reassessing not only our view of the genetic and pathophysiological diversity of these disorders, but also the predominant strategies for SZ therapeutics; indeed, our field is gaining awareness that we must move away from a "find what's broke and fix it" approach, toward identifying spared neural and cognitive function in SZ patients, and matching these residual neural assets with learning-based therapies. Perhaps, construct-valid models that identify evidence of "spared function" in neural substrates might reveal opportunities for future therapeutics and allow us to study these substrates at a mechanistic level to maximize opportunities for neuroplasticity. Such an effort will require a retooling of our models, and more importantly, a re-evaluation of their utility. For animal models to remain relevant in the search for schizophrenia therapeutics, they will need to focus less on what is valid and focus more on what is useful.

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“…Although the ability of dizocilpine, the prototypical NMDA receptor antagonist, to increase dopaminergic activity has been well described (Hiramatsu et al, 1989;Rao et al, 1990), many observations confirm that the mechanism through which it produces a robust disruption in PPI is unlikely to be mediated by D 2 receptors. A large body of literature shows D 2 selective antagonists are unable to reverse PPI disruption induced by NMDA receptor antagonists Johansson et al, 1994). Moreover, although several studies report atypical antipsychotics are effective against deficits caused by NMDA receptor antagonists Bakshi et al, 1994), the assumption remains debated in view of conflicting results on the ability of clozapine and other atypical antipsychotics to antagonize dizocilpine-mediated PPI disruption (Hoffman et al, 1993;Bast et al, 2000).…”

Section: Introductionmentioning

confidence: 99%

Activation of D1, but not D2 Receptors Potentiates Dizocilpine-Mediated Disruption of Prepulse Inhibition of the Startle

Bortolato¹,

Aru²,

Fà³

et al. 2004

Neuropsychopharmacol

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Although substantial evidence has shown interactions between glutamatergic and dopaminergic systems play a cardinal role in the regulation of attentional processes, their involvement in informational filtering has been poorly investigated. Chiefly, little research has focused on functional correlations between the dopaminergic system and the mechanism of action of N-methyl-D-aspartate (NMDA) receptor antagonists on sensorimotor gating. The present study was targeted at evaluating whether the activation of D 1 and D 2 receptors is able to interact with the disruption of prepulse inhibition (PPI) of startle mediated by dizocilpine, a selective, noncompetitive NMDA receptor antagonist. We tested the effects of SKF 38393 ((7)-1-phenyl-2,3,4,5-tetrahydro-(1H)-3-benzazepine-7,8-diol) (10 mg/kg, s.c.), a selective D 1 agonist, and quinpirole (0.3, 0.6 mg/kg, s.c.), a D 2 agonist, in rats, per se and in cotreatment with different doses of dizocilpine, ranging from 0.0015 to 0.15 mg/kg (s.c.). Subsequently, the effect of the D 1 antagonist SCH 23390 ((R)-( þ )-7-chloro-8-hydroxy-3-methyl-1-phenyl-2,3,4,5-tetrahydro-1H-3-benzazepine) (0.05, 0.1 mg/kg, s.c.) on PPI disruptions mediated by dizocilpine and by combination of dizocilpine and SKF 38393 was tested. Two further experiments were performed to verify whether the synergic effect of the D 1 agonist with dizocilpine was counteracted by effective doses of haloperidol (0.1, 0.5 mg/kg, i.p.) and clozapine (5, 10 mg/kg, i.p.). All experiments were carried out using standard procedures for the assessment of PPI of the acoustic startle reflex. SKF 38393, while unable to impair sensorimotor gating alone, induced PPI disruption in cotreatment with 0.05 and 0.15 mg/kg of dizocilpine, both ineffective per se. Furthermore, this effect was reversed by SCH 23390, but not by haloperidol or clozapine. Conversely, no synergistic effect was exhibited between quinpirole and dizocilpine, at any given dose. These findings suggest that D 1 , but not D 2 receptors, enhance the disruptive effect of dizocilpine on PPI.

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The atypical antipsychotic, remoxipride, blocks phencyclidine-induced disruption of prepulse inhibition in the rat

Cited by 77 publications

References 27 publications

Inbred strain differences in prepulse inhibition of the mouse startle response

Inbred strain differences in prepulse inhibition of the mouse startle response

Animal Models of Deficient Sensorimotor Gating in Schizophrenia: Are They Still Relevant?

Activation of D1, but not D2 Receptors Potentiates Dizocilpine-Mediated Disruption of Prepulse Inhibition of the Startle

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