Disruption of Latent Inhibition in Rats with Postnatal Hippocampal Lesions

Grecksch, Gisela; Hg, Bernstein; Becker, Axel; Höllt, Volker; Bogerts, Bernhard

doi:10.1016/s0893-133x(98)00081-5

Cited by 96 publications

(46 citation statements)

References 41 publications

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“…Another series of studies have focused on neonatal damage of restricted brain regions in rats (Lipska et al 1993;Flores et al 1996a;Chambers et al 1996;Wan et al 1996Wan et al , 1998Wan and Corbett 1997;Brake et al 1999, Black et al 1998Grecksch et al 1999;Schroeder et al 1999) and in monkeys (Beauregard and Bachevalier 1996;Bertolino et al 1997;Saunders et al 1998;Bachevalier et al 1999). The main objective of many of these studies is to disrupt development of the hippocampus, a brain area consistently implicated in human schizophrenia (Falkai and Bogerts 1986;Jeste and Lohr 1989;Bogerts et al 1990;Suddath et al 1990;Eastwood et al 1995Eastwood et al , 1997Eastwood andHarrison 1995, 1998;Weinberger 1999), and thus disrupt development of the widespread cortical and subcortical circuitry in which the hippocampus participates.…”

Section: Neonatal Brain Lesionsmentioning

confidence: 99%

“…In adolescence and adulthood (postnatal day 56 and older), lesioned animals display markedly changed behaviors thought to be primarily linked to increased mesolimbic/nigrostriatal dopamine transmission (motor hyperresponsiveness to stress and stimulants, enhanced stereotypies). They also show enhanced sensitivity to glutamate antagonists (MK-801 and PCP), deficits in PPI and latent inhibition, impaired social behaviors and working memory problems (Lipska and Weinberger 1993, 1994a, 1994bLipska et al 1995a;Grecksch et al 1999;Al-Amin et al in press;Hori et al 1999), phenomena showing many parallels with schizophrenia.…”

Section: Neonatal Brain Lesionsmentioning

confidence: 99%

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To Model a Psychiatric Disorder in Animals Schizophrenia As a Reality Test

Lipska

Weinberger

2000

Neuropsychopharmacology

588

386

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Animal modeling has been instrumental in dissectingAnimal models are important developments in investigations of the mechanisms underlying a human disease and the design of new treatments. This is true for many diseases, but generally not for mental disorders, whose modeling in experimental animals has often been regarded as a highly controversial or outright heretic idea. An example of a particularly formidable challenge for animal modeling is schizophrenia, a complex disorder of unknown origin, characterized by abnormalities of uniquely human behaviors in the realms of perception, thinking and the experience of emotions, and whose onset is virtually restricted to young adulthood. Schizophrenia is such an inherently human disease that reproducing its most prominent symptoms-hallucinations, delusions and thought disorder-in a rodent or even in a non-human primate seems doomed. However, recent new evidence about the neurobiology of the condition has generated new avenues of animal research. In this perspective article, we highlight recent achievements in the efforts to model the neurobiology of schizophrenia in animals, consider limitations inherent in any heuristic animal model of this and probably other psychiatric disorders, and discuss the usefulness of a new generation of animal models for testing particular hypotheses about etiology and pathophysiology of schizophrenia.

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Section: Neonatal Brain Lesionsmentioning

confidence: 99%

Section: Neonatal Brain Lesionsmentioning

confidence: 99%

To Model a Psychiatric Disorder in Animals Schizophrenia As a Reality Test

Lipska

Weinberger

2000

Neuropsychopharmacology

588

386

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“…The nVHLX model, which involves permanent excitotoxic damage to the VH during a sensitive period in early postnatal development, results in a wide range of neuronal abnormalities hypothesized to contribute to the development of SZ, including: decreases in dendritic spine density in NAC and PFC (Flores et al, 2005); abnormal activation of PFC and NAC neurons in response to mesocorticolimbic stimulation (Goto and O'Donnell, 2002;O'Donnell et al, 2002); and altered regulation of cortical cholinergic activity (Alexander et al, 2009;Brooks et al, 2011;Laplante et al, 2004). The nVHLX model also reveals a range of SZ-like cognitive impairments, including: reductions in prepulse inhibition (Le Pen and Moreau, 2002) and latent inhibition (Grecksch et al, 1999); deficits in working memory (Lipska et al, 2002a;Brady et al, 2010) and cognitive flexibility (Marquis et al, 2008;Brady, 2009) tasks, which are known to be heavily reliant on appropriate hippocampal-PFC-NAC interactions (Chambers et al, 1996;Floresco et al, 2009).…”

Section: Introductionmentioning

confidence: 99%

Transient Inactivation of the Neonatal Ventral Hippocampus Impairs Attentional Set-Shifting Behavior: Reversal with an α7 Nicotinic Agonist

Brooks

Pershing

Thomsen

et al. 2012

Neuropsychopharmacol

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Cognitive deficits represent a core symptom cluster in schizophrenia that are thought to reflect developmental dysregulations within a neural system involving the ventral hippocampus (VH), nucleus accumbens (NAC), and prefrontal cortex (PFC). The present experiments determined the cognitive effects of transiently inactivating VH in rats during a sensitive period of development. Neonatal (postnatal day 7, PD7) and adolescent (PD32) male rats received a single bilateral infusion of saline or tetrodotoxin (TTX) within the VH to transiently inactivate local circuitry and efferent outflow. Rats were tested as adults on an attentional set-shifting task. Performance in this task depends upon the integrity of the PFC and NAC. TTX infusions did not affect the initial acquisition or ability to learn an intradimensional shift. However, TTX rats required a greater number of trials than did controls to acquire the first reversal and extradimensional shift (ED) stages. These impairments were age and region-specific as rats infused with TTX into the VH at PD32, or into the dorsal hippocampus at PD7, exhibited performance in the task similar to that of controls. Finally, acute systemic administration of the partial a7 nicotinic acetylcholine receptor (nAChR) agonist SSR 180711 (3.0 mg/kg) eliminated the TTX-induced performance deficits. Given that patients with schizophrenia exhibit hippocampal pathophysiology and deficits in the ED stages of set-shifting tasks, our results support the significance of transient hippocampal inactivation as an animal model for studying the cognitive impairments in schizophrenia as well as the pro-cognitive therapeutic potential of a7 nAChR agonists.

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“…NVHL rats have been studied by several groups as a comprehensive animal model of schizophrenia. NVHL rats show post-adolescent onset of neurolepticresponsive, positive-like symptoms, such as hyper-responsivity of dopamine-mediated behaviors (Lipska et al 1993;Lipska and Weinberger 1994) accompanied by a number of schizophrenia-related cognitive and negative-like symptoms Chambers et al 1996;Grecksch et al 1999;Lipska et al 1995). In applying this animal model toward understanding increased substance use disorder (SUD) comorbidity in schizophrenia, NVHL rats show increased vulnerability to developing an addicted phenotype in acquisition, maintenance and post-withdrawal phases of COC self-administration (Chambers and Self 2002).…”

Section: Introductionmentioning

confidence: 99%

Natural reward-related learning in rats with neonatal ventral hippocampal lesions and prior cocaine exposure

et al. 2004

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Rational-Psychostimulant injections in rats have been shown to alter future performance in natural reward conditioning. These effects may represent a persistent impact of drugs on neurocircuits that interface cognitive and motivational processes, which may be further altered in neuropsychiatric conditions that entail increased addiction vulnerability.Objective-This study investigated whether a rat model of schizophrenia with cocaine addiction vulnerability shows altered natural reward conditioning with or without prior cocaine exposure.Methods-Adult rats with SHAM or neonatal ventral hippocampal lesions were given cocaine (15 mg/kg per day for 5 days) or saline injections, followed 7 days later by natural reward-conditioned learning. Over ten daily sessions, water-restricted rats were assessed for durations of head entries into a magazine during random water presentations, a conditioning stimulus phase predictive of the water reward, and an "inappropriate" phase when conditioning stimuli were absent and reward presentation would be delayed.Results-Over repeated sessions, lesioned and SHAM rats showed similar reductions in total magazine entry durations, with similar increases in the allocations of entry times during the water presentation. However, lesioned rats, especially those exposed to cocaine, demonstrated reduced allocations of magazine entry times during the conditioning stimulus phase, and increased allocations during the inappropriate phase.Conclusions-Intact natural reward motivation accompanied by deficient learning of complex contingencies to guide efficient reward approach may represent a form of impulsivity as an addiction vulnerability trait marker in an animal model of schizophrenia.

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Disruption of Latent Inhibition in Rats with Postnatal Hippocampal Lesions

Cited by 96 publications

References 41 publications

To Model a Psychiatric Disorder in Animals Schizophrenia As a Reality Test

To Model a Psychiatric Disorder in Animals Schizophrenia As a Reality Test

Transient Inactivation of the Neonatal Ventral Hippocampus Impairs Attentional Set-Shifting Behavior: Reversal with an α7 Nicotinic Agonist

Natural reward-related learning in rats with neonatal ventral hippocampal lesions and prior cocaine exposure

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