Latent inhibition and schizophrenia

Lubow, R. E.; Weiner, Ina; Schlossberg, Anat; Baruch, Ilan

doi:10.3758/bf03334742

Cited by 152 publications

(76 citation statements)

References 21 publications

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“…It is nonetheless not inconsistent with the alternative view that this represents an indication of enhanced behavioral switching in schizophrenia patients (Weiner, 1990). In animals, LI is abolished by amphetamine and enhanced by both typical and atypical neuroleptics (Weiner and Feldon, 1987;Christison et al, 1988;Feldon and Weiner, 1991;Peters and Joseph, 1993;Dunn et al, 1993), suggesting that LI may constitute an animal model of the attentional deficits associated with schizophrenia (Solomon et al, 1981;Lubow et al, 1987;Weiner, 1990;Feldon and Weiner, 1991;Gray et al, 1991;Moser et al, 2000). The suggestion that elevated levels of glycine can be effective against schizophrenia-related cognitive symptoms has led us to expect a possible LI-enhancing phenotype in the mutant mice with protocols suitable for the demonstration of such an effect.…”

Section: Figurementioning

confidence: 77%

Disruption of Glycine Transporter 1 Restricted to Forebrain Neurons Is Associated with a Procognitive and Antipsychotic Phenotypic Profile

Yee¹,

Balic²,

Singer³

et al. 2006

J. Neurosci.

133

162

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The NMDA receptor is thought to play a central role in some forms of neuronal plasticity, including the induction of long-term potentiation. NMDA receptor hypofunction can result in mnemonic impairment and has been implicated in the cognitive symptoms of schizophrenia. The activity of NMDA receptors is controlled by its endogenous coagonist glycine, and a local elevation of glycine levels is expected to enhance NMDA receptor function. Here, we achieved this by the generation of a novel mouse line (CamKII␣Cre;Glyt1tm1.2fl/ fl) with a neuron and forebrain selective disruption of glycine transporter 1 (GlyT1). The mutation led to a significant reduction of GlyT1 and a corresponding reduction of glycine reuptake in forebrain samples, without affecting NMDA receptor expression. NMDA (but not AMPA) receptor-evoked EPSCs recorded in hippocampal slices of mutant mice were 2.5 times of those recorded in littermate controls, suggesting that neuronal GlyT1 normally assumes a specific role in the regulation of NMDA receptor responses. Concomitantly, the mutants were less responsive to phencyclidine than controls. The mutation enhanced aversive Pavlovian conditioning without affecting spontaneous anxiety-like behavior in the elevated plus maze and augmented a form of attentional learning called latent inhibition in three different experimental paradigms: conditioned freezing, conditioned active avoidance, conditioned taste aversion. The CamKII␣Cre; Glyt1tm1.2fl/fl mouse model thus suggests that augmentation of forebrain neuronal glycine transmission is promnesic and may also offer an effective therapeutic intervention against the cognitive and attentional impairments characteristic of schizophrenia.

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Section: Figurementioning

confidence: 77%

Disruption of Glycine Transporter 1 Restricted to Forebrain Neurons Is Associated with a Procognitive and Antipsychotic Phenotypic Profile

Yee¹,

Balic²,

Singer³

et al. 2006

J. Neurosci.

133

162

View full text Add to dashboard Cite

show abstract

“…In the first LI-schizophrenia study, Lubow, Weiner, Schlossberg, and Baruch (1987) investigated LI effects in paranoid and nonparanoid patients. Based on the animal literature, they expected to find attenuated LI in the two patient groups compared to healthy controls.…”

Section: Latent Inhibition and Schizophreniamentioning

confidence: 99%

“…As opposed to acute nonmedicated patients, chronic medicated schizophrenics exhibit intact LI (Baruch et al, 1988a;Gray, Hemsley, et al, 1992;Leumann, Feldon, Vollenweider, & Ludewig, 2002;Lubow et al, 1987). However, a recent study by Cohen et al (2004) suggests that the LI effect in schizophrenia is even more complex.…”

Section: Latent Inhibition and Schizophreniamentioning

confidence: 99%

Intelligence and Cognitive Control

Chuderski

Nęcka²

2010

Handbook of Individual Differences in Cognition

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“…Disruption of LI has been observed in nonmedicated acute schizophrenics (4) as well as animals and humans treated with the psychotomimetic drug amphetamine (14,22,49,(64)(65)(66)(67). Medicated schizophrenic patients do not demonstrate disrupted LI (4,37). In addition, antipsychotic medications reverse amphetamine-induced disruption of LI in animals (49,68), and can enhance LI on their own (11,15).…”

Section: Latent Inhibitionmentioning

confidence: 99%

The Delayed Effects of DTG and MK-801 on Latent Inhibition in a Conditioned Taste-Aversion Paradigm

Turgeon¹,

Auerbach²,

Duncan-Smith³

et al. 2000

Pharmacology Biochemistry and Behavior

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. The delayed effects of DTG and MK-801 on latent inhibition in a conditioned taste-aversion paradigm. PHARMACOL BIOCHEM BEHAV 66 (3) 533-539, 2000.-The delayed effects of phencyclidine (PCP) have been shown to disrupt latent inhibition (LI) in a conditioned taste-aversion paradigm. In an attempt to understand the mechanism of this disruption, the delayed effects of the selective sigma receptor agonist 1,3-Di(2-tolyl)guanidine (DTG) and the selective NMDA receptor antagonist MK-801 on latent inhibition were assessed in the same paradigm. Water-deprived male rats were allowed access to either water (nonpreexposed; NPE) or 5% sucrose (preexposed; PE) for 30 min on 2 consecutive days. On the third day, animals were allowed access to sucrose and subsequently injected with lithium chloride. On the forth day, animals were allowed access to both sucrose and water. LI was assessed by comparing the percent sucrose consumed in PE and NPE groups on the fourth day. DTG (1.0, 5.0, or 10.0 mg/kg), MK-801 (0.5, 1.0, or 2.0 mg/kg), or vehicle was administered IP 20 h before preexposure (days 1 and 2) and conditioning (day 3). In vehicle-treated groups, PE animals consumed a significantly higher percent sucrose on the test day than NPE animals, indicating the presence of LI. DTG (10.0 mg/kg) and MK-801 (2.0 mg/kg) decreased the percent sucrose consumed by animals in the PE group to the level observed in the NPE group, indicating disrupted LI. However, this dose of MK-801 was found to produce a decrease in percent sucrose consumed in PE animals not treated with lithium chloride, indicating that the decrease observed in the LI paradigm could be due to MK-801-induced decrease in taste preference for sucrose rather than a disruption of LI. Lower doses of MK-801 that did not produce a decrease in taste preference for sucrose did not significantly disrupt LI. None of the doses of DTG tested altered taste preference for sucrose. These data suggest a role for sigma receptors in the previously observed PCP-induced disruption of LI. LATENT inhibition (LI) is the impaired acquisition of a conditioned response to a stimulus that has been previously presented without reinforcement (35). LI is thought to be a measure of an organism's capacity to ignore irrelevant stimuli, and has been demonstrated in a variety of species including humans (4,35,36). Disruption of LI has been observed in nonmedicated acute schizophrenics (4) as well as animals and humans treated with the psychotomimetic drug amphetamine (14,22,49,(64)(65)(66)(67). Medicated schizophrenic patients do not demonstrate disrupted LI (4,37). In addition, antipsychotic medications reverse amphetamine-induced disruption of LI in animals (49,68), and can enhance LI on their own (11,15). These observations suggest that the disruption of LI is a useful animal model for this specific attentional deficit seen in schizophrenia (12,15). Phencyclidine (PCP) is a drug that can produce a psychotomimetic effect in humans (3,28,38) as well as a number of behavioral and cognitive changes in animals...

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Latent inhibition and schizophrenia

Abstract: The phenomenon of latent inhibition Show more

Cited by 152 publications

References 21 publications

Disruption of Glycine Transporter 1 Restricted to Forebrain Neurons Is Associated with a Procognitive and Antipsychotic Phenotypic Profile

Disruption of Glycine Transporter 1 Restricted to Forebrain Neurons Is Associated with a Procognitive and Antipsychotic Phenotypic Profile

Intelligence and Cognitive Control

The Delayed Effects of DTG and MK-801 on Latent Inhibition in a Conditioned Taste-Aversion Paradigm

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