The amphetamine-induced sensitized state as a model of schizophrenia

Featherstone, Robert E.; Kapur, Shitij; Fletcher, Paul

doi:10.1016/j.pnpbp.2007.08.025

Cited by 199 publications

(131 citation statements)

References 211 publications

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“…This finding contrasts with the prior results indicating that only clozapine, but not haloperidol, attenuates the behavioral effects of phencylcidine (Abdul-Monim et al, 2006;Dunn and Killcross, 2006). While phencylcidine/ketamine models have been productively employed to model other cognitive deficits associated with schizophrenia (Abdul-Monim et al, 2006;Dunn and Killcross, 2006;Jentsch and Roth, 1999), the present results correspond with the view that with respect to the modeling of specifically the attentional impairments of schizophrenia, phencylcidine/ketamine models may be less useful (Featherstone et al, 2007;Fletcher et al, 2005;Nelson et al, 2002). Given that the available clinical evidence does not suggest robust differences between the pro-cognitive efficacy of low doses of haloperidol and clozapine (see 'Introduction'), our results suggest that the present experimental paradigm is capable of reproducing these effects, thereby meeting an available criterion for predictive validity (Hagan and Jones, 2005).…”

Section: Discussioncontrasting

confidence: 91%

“…Repeated administration of psychostimulants has been shown to model important neurobiological, behavioral, and cognitive aspects of schizophrenia, including a sensitized mesolimbic dopamine system and impairments in attentional performance Goldman-Rakic, 1999, 2003;Castner et al, 2004Castner et al, , 2005Crider et al, 1982;Dalley et al, 2005;Featherstone et al, 2007;Fletcher et al, 2005Fletcher et al, , 2007Kapur, 2003;Martinez et al, 2005;Robinson and Becker, 1986;Russig et al, 2002;Tenn et al, 2003Tenn et al, , 2005. Based on extensive evidence indicating the crucial role of the cortical cholinergic input system for attention Parikh et al, 2007;Sarter et al, 2006Sarter et al, , 2005a, the attentional symptoms of schizophrenia have been proposed to be mediated via abnormalities in the regulation and activity of this neuronal system Raedler et al, 2003Raedler et al, , 2007Sarter et al, 2005b).…”

Section: Introductionmentioning

confidence: 99%

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Detection of the Moderately Beneficial Cognitive Effects of Low-Dose Treatment with Haloperidol or Clozapine in an Animal Model of the Attentional Impairments of Schizophrenia

Martı́nez

Sarter

2007

Neuropsychopharmacol

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The absence of effective cognition enhancers for the treatment of patients with schizophrenia limits the validation of animal models and behavioral tests used for drug finding and characterization. However, low doses of haloperidol and clozapine were documented to produce moderately beneficial effects in patients. Therefore, this experiment was designed to determine the attentional effects of such treatments in a repeated-amphetamine (AMPH) animal model. Animals were trained in an operant-sustained attention task and underwent a 40-day pretreatment period with saline or increasing doses (1-10 mg per kg) of AMPH. After regaining baseline performance following 10 days of saline treatment, animals were treated with haloperidol (0.025 mg per kg), clozapine (2.5 mg per kg), or vehicle for 10 days. Furthermore, the effects of AMPH challenges (1.0 mg per kg) were assessed. In AMPH-pretreated animals, the administration of AMPH challenges resulted in the disruption of attentional performance. Treatment with haloperidol and clozapine attenuated the detrimental performance effects of these challenges, with clozapine exhibiting more robust attenuation. Furthermore, clozapine, but not haloperidol, impaired the performance of control animals. In contrast, the performance of AMPH-pretreated animals remained unaffected by clozapine. As this animal model detects the moderately beneficial cognitive effects of haloperidol and clozapine, it may be useful for preclinical research designed to detect and characterize treatments for the cognitive symptoms of schizophrenia.

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Section: Discussioncontrasting

confidence: 91%

Section: Introductionmentioning

confidence: 99%

Detection of the Moderately Beneficial Cognitive Effects of Low-Dose Treatment with Haloperidol or Clozapine in an Animal Model of the Attentional Impairments of Schizophrenia

Martı́nez

Sarter

2007

Neuropsychopharmacol

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“…In their review, Featherstone et al (2007; this issue) present compelling evidence that the amphetamineinduced sensitized state models the positive symptoms and cognitive deficits observed in schizophrenia. They describe a number of rodent experiments showing that exposure to sensitizing amphetamine injection regimens produces reduced prepulse inhibition and disrupted latent inhibition as well as impairments in tasks that require sustained attention, extradimensional shifts and reversal learning.…”

Section: Nih-pa Author Manuscriptmentioning

confidence: 99%

Sensitization, drug addiction and psychopathology in animals and humans

Vezina

2007

Progress in Neuro-Psychopharmacology and Biological Psychiatry

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The past 30 years have witnessed a substantial and growing interest in drug sensitization, particularly relating to the psychoactive and appetitive properties of psychostimulant and opiate drugs. It is now well established that rats repeatedly exposed to amphetamine, for example, will exhibit an enhanced -sensitized -locomotor response when subsequently challenged with the drug some time later. It is also well established that in these rats, the ability of amphetamine to increase extracellular levels of dopamine (DA) in forebrain is also enhanced. There have been many reports of such effects with a number of abused drugs from these two drug classes (for references and critical reviews of the preclinical literature, see Kalivas and Stewart, 1991;Vanderschuren and Kalivas, 2000;Vezina, 2004). Of particular note, these effects are long lasting in the rat: up to one year following drug exposure for locomotion (Paulson et al., 1991) and up to three months for DA overflow (Hamamura et al., 1991) -the longest withdrawal periods tested. Indeed, amphetamine-induced nucleus accumbens DA overflow increases with time after exposure to the drug (Figure 1).Given the critical role played by the mesoaccumbens DA pathways in the generation of appetitive behaviors including the pursuit and self-administration of abused drugs, it follows that altered activity in these pathways could affect the appetitive behavioral output of the organism. The incrementing and long lasting changes in nucleus accumbens DA overflow observed in rats following exposure to sensitizing drug regimens suggest that such effects on behavior can be long lasting. Such possibilities have fueled a large number of systems, cellular and molecular biological level investigations of the mechanisms that might underlie altered reactivity in midbrain DA neurons and those systems they interact with. On the other hand, while there is general agreement that drug sensitization can be demonstrated in some preparations, there has been less consensus as to whether and how sensitization might impact the generation of appetitive behaviors either within or between species.This special issue highlights evidence obtained in rodents, non-human primates and humans that supports a role for sensitization in the generation of states that promote or are related to enhanced drug taking. This evidence is reviewed in the context of different data sets, interpretations and models from the clinical and pre-clinical literature with the goal of understanding and integrating sometimes apparently disparate views. Drug addiction is characterized by compulsive drug taking that persists despite escalating costs and adverse consequences. Over the past 20 years, sensitization of the appetitive effects of drugs has emerged as a possible mechanism underlying enhanced drug use Berridge, 1993, 2003). However, a review of the pre-clinical literature reveals findings Correspondence: Department of Psychiatry, The University of Chicago, 5841 S. Maryland Avenue, MC3077, Chicago, IL 60637, TEL: 773/702-2890,...

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“…Many drugs of abuse may act via the common mechanism of sensitization addiction and psychosis. In humans and animals, repeated exposure to psychostimulants induces a sensitized state [150]. Sensitized animals share a number of neurobiological changes such as long term alterations of mesolimbic and prefrontal dopaminergic neurotransmission while also expressing behavioral abnormalities [150].…”

Section: Administration Of Thc or Cannabis Elicitsmentioning

confidence: 99%

Epigenetic epidemiology in psychiatry: A translational neuroscience perspective

Pishva

Kenis

Lesch

et al. 2012

Translational Neuroscience

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Introductiondifferential epigenetic profiles) for epigenetic involvement in the most prevalent and severe psychiatric illnesses. We will end the article by discussing current research challenges in epigenetic epidemiology and neuroscience, and we propose that more studies combining epidemiological and neuroscience approaches in studying epigenetics are needed to improve our understanding of the role of the epigenetic machinery in the etiologies of psychiatric disorders. Besides robust changes in reprogramming of genomic methylation patterns in germline cells as well as in pre-implantation embryos [78]. In autism, a 10-year increase in paternal age (independent of maternal age) was associated with a 22% increased risk for autism (independent of paternal age) while a 10-year increase in maternal age has been associated with a 38% increased risk for developing the disorder [78,79], which is in line with other findings reporting associations between parental ages and autism [80][81][82]. A recent metaanalysis on the association between paternal age and schizophrenia reported that both advanced paternal age (>/=30) and younger paternal age (<25) may increase the risk of schizophrenia, with further analyses indicating that younger paternal age may be associated with particularly an increased risk in male but not female offspring [83]. Given these effects of paternal (and maternal age) on risk of several psychiatric disorders, one could speculate that Epigenetic mechanisms Epigenetics and sex differences in psychiatric disorders Environmental epigenetic in psychiatric disordersA wealth of epidemiologic evidence indicates that environmental exposures influence susceptibility to disease in later life [19,49].

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The amphetamine-induced sensitized state as a model of schizophrenia

Cited by 199 publications

References 211 publications

Detection of the Moderately Beneficial Cognitive Effects of Low-Dose Treatment with Haloperidol or Clozapine in an Animal Model of the Attentional Impairments of Schizophrenia

Detection of the Moderately Beneficial Cognitive Effects of Low-Dose Treatment with Haloperidol or Clozapine in an Animal Model of the Attentional Impairments of Schizophrenia

Sensitization, drug addiction and psychopathology in animals and humans

Epigenetic epidemiology in psychiatry: A translational neuroscience perspective

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