“Early” and “Late” Effects of Sustained Haloperidol on Apomorphine- and Phencyclidine-induced Sensorimotor Gating Deficits

Martinez, Z.A.; Oostwegel, Jeff L.; Geyer, Mark A.; Ellison, Gaylord; Swerdlow, Neal R.

doi:10.1016/s0893-133x(00)00147-0

Cited by 38 publications

(26 citation statements)

References 43 publications

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“…Indeed, antipsychotic medicines may decrease PPI deficits when administered to patients with schizophrenia . Given the fact that chronic administration is normally associated with the clinical properties of antipsychotic drugs, the acute behavioral effects in rodents may not fully mimic the clinical properties of these drugs Martinez et al, 2000). Interestingly, a number of studies which have directly compared acute vs chronic treatment with both typical and atypical antipsychotics have demonstrated that acute may be more effective than chronic administration at reducing PPI deficits induced by pharmacological or environmental manipulations (Andersen and Pouzet, 2001).…”

Section: Discussionmentioning

confidence: 99%

Prepulse Inhibition Deficits in GAD65 Knockout Mice and the Effect of Antipsychotic Treatment

Heldt

Green

Ressler

2004

Neuropsychopharmacol

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Recent postmortem studies in humans suggest that defects in GABAergic neurotransmission might contribute to the neuropathology associated with schizophrenia. Disturbances in GABAergic systems may also contribute to the sensorimotor gating deficits classically observed in schizophrenic patients, including deficits in prepulse inhibition (PPI). To explore the relationship, the current study examined the integrity of PPI and startle habituation in knockout (KO) mice that lack the GABA synthesizing enzyme glutamic acid decarboxylase 65 (GAD 65). GAD65 KO mice displayed normal baseline and habituated startle responses, which did not differ from GAD65 wild-type (WT) or heterozygous (HET) mice. However, GAD65 KO mice showed robust deficits in PPI which were reversed by the atypical antipsychotic agent clozapine. These results lend support to the view that abnormalities in GABAergic systems might contribute to the basic pathophysiological mechanisms in schizophrenia.

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Section: Discussionmentioning

confidence: 99%

Prepulse Inhibition Deficits in GAD65 Knockout Mice and the Effect of Antipsychotic Treatment

Heldt

Green

Ressler

2004

Neuropsychopharmacol

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“…First, the effects seen in normal subjects with one single acute dose of drug are unlikely to reflect those seen with chronic use in schizophrenic populations. In rats, DA manipulations involving repeated exposures are known to produce different effects on PPI from those seen with single administration (Taylor et al 1995;Martinez et al 2000). Further, unless deficits are first induced by some pharmacological or experimental means, antipsychotic efficacy, which should take the form of deficit correction, cannot be determined in normal subjects.…”

Section: Typical Antipsychoticsmentioning

confidence: 99%

Effects of typical and atypical antipsychotics on prepulse inhibition in schizophrenia: a critical evaluation of current evidence and directions for future research

Kumari¹,

Sharma²

2002

Psychopharmacology

154

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Prepulse inhibition (PPI) of the startle response refers to an attenuation in response to a strong stimulus (pulse) if this is preceded shortly by a weak non-startling stimulus (prepulse). PPI provides a simple operational measure of sensorimotor gating, serving to prevent the interruption of ongoing perceptual and early sensory analysis. In accord with postulated deficits in early stages of information processing, there is ample evidence that PPI is disrupted in individuals with schizophrenia. PPI in animals is thought to represent a well-validated model for evaluating potential new treatments for schizophrenia. Currently, available data on the differential effects of typical and atypical antipsychotics suggest that atypical antipsychotics, in particular clozapine and risperidone, may be more effective than typical antipsychotics in improving PPI deficits in schizophrenia. However, studies have so far used small samples and/or between-subjects designs, and not examined the effects of other concomitant medications that may also influence PPI. The directions are identified for further applications of this model using within-subjects longitudinal designs and reasonable sample sizes to establish superiority of particular atypical antipsychotics over typical antipsychotics in improving PPI in schizophrenic populations.

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“…For example, acute treatment with clozapine and olanzapine enhanced NMDA-evoked electrophysiological responses, but chronic treatment with the drugs reduced NMDA receptor sensitivity (Arvanov and Wang, 1999;Jardemark et al, 2000). Also, chronic haloperidol was shown to reduce PCP-induced alterations in PPI under conditions where acute administration of this typical antipsychotic did not affect PCP-induced PPI deficits (Pietraszek and Ossowska, 1998;Martinez et al, 2000).…”

mentioning

confidence: 99%

Chronic Administration of Haloperidol and Olanzapine Attenuates Ketamine-Induced Brain Metabolic Activation

Duncan

Miyamoto²,

Lieberman³

2003

J Pharmacol Exp Ther

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The fact that chronic administration of typical and atypical antipsychotic drugs is required for optimal therapeutic response suggests that drug-induced adaptive neurochemical changes contribute to their mechanism of action. In the present study, the effects of chronic and acute haloperidol and olanzapine were compared on ketamine-induced activation of select brain regions, as reflected by altered regional 14 C-2-deoxyglucose (2-DG) uptake. Rats were injected once daily with haloperidol (1 mg/kg) or olanzapine (10 mg/kg) for 21 days, and 20 to 24 h after the final injection was challenged with saline or ketamine (25 mg/kg). The washout period was used to test the effects of chronic drug treatment without the influence of acute drug administration. In vehicle-treated rats, ketamine increased 2-DG uptake in select brain regions, including medial prefrontal cortex, nucleus accumbens, caudate putamen, stratum lacunosum-moleculare of hippocampus, and basolateral nucleus of the amygdala. This selective activation was attenuated by prior chronic treatment with both haloperidol and olanzapine. After acute treatment, olanzapine, but not haloperidol, blocked the ketamine-induced activation of 2-DG uptake. These data suggest that both haloperidol and olanzapine can induce adaptive responses that counteract effects of ketamine. However, the differences observed in the acute effects of the two drugs in the ketamine challenge model suggest that different mechanisms could be responsible for their common chronic action of attenuating ketamine-induced brain metabolic activation.Psychotomimetic effects of NMDA receptor antagonists in humans suggest that reduced NMDA receptor function may contribute to the pathophysiology of schizophrenia. Antagonists of the NMDA receptor such as ketamine and phencyclidine (PCP) induce a spectrum of behavioral effects that mimic positive, negative, and cognitive symptoms of schizophrenia (Luby et al., 1959;Cohen et al., 1962;Krystal et al., 1994;Malhotra et al., 1996;Lahti et al., 2001). Furthermore, in stabilized schizophrenic patients, ketamine can precipitate positive symptoms that are remarkably similar to those experienced during active phases of the patient's illness (Lahti et al., 1995a,b;Malhotra et al., 1997). The human experience with NMDA antagonists provides the foundation for the NMDA receptor hypofunction hypothesis of schizophrenia (Javitt and Zukin, 1991;Olney and Farber, 1995;Coyle, 1996).Preclinical studies of the effects of antipsychotic drugs in paradigms involving challenge with NMDA receptor antagonists provide support for the NMDA receptor hypofunction hypothesis. Extensive preclinical data demonstrate differential effects of acutely administered "typical" antipsychotics and "atypical" antipsychotic drugs on responses to NMDA antagonists. Although there is no universal consensus on precise definitions for typical and atypical antipsychotics, the typical drugs are generally considered those whose primary mechanism is D2 dopamine blockade (e.g., haloperidol, chlorproma...

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“Early” and “Late” Effects of Sustained Haloperidol on Apomorphine- and Phencyclidine-induced Sensorimotor Gating Deficits

Abstract: Both dopamine (DA) agonists and NMDA antagonists produce prepulse inhibition (PPI) deficits in rats that

Cited by 38 publications

References 43 publications

Prepulse Inhibition Deficits in GAD65 Knockout Mice and the Effect of Antipsychotic Treatment

Prepulse Inhibition Deficits in GAD65 Knockout Mice and the Effect of Antipsychotic Treatment

Effects of typical and atypical antipsychotics on prepulse inhibition in schizophrenia: a critical evaluation of current evidence and directions for future research

Chronic Administration of Haloperidol and Olanzapine Attenuates Ketamine-Induced Brain Metabolic Activation

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