Facilitation of the expression but not the acquisition of latent inhibition by haloperidol in rats

Weiner, Ina; Feldon, Joram; Katz, Y.

doi:10.1016/0091-3057(87)90112-2

Cited by 134 publications

(35 citation statements)

References 34 publications

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“…Figure 5 (right) shows the model's predictions under these conditions. Figure 5 (left) shows experimental data from a similar LI experiment to that described above, except that an APD (haloperidol) rather than amphetamine was administered during both preexposure and subsequent avoidance conditioning (Weiner et al, 1987). Both the experiment and the simulation show facilitation of LI under APD.…”

Section: Resultsmentioning

confidence: 92%

“…Figure 5 The LI effect, and its enhancement under the APD haloperidol, shown experimentally (left) and within the TD model (right). The experimental results are adapted from (Weiner et al, 1987). The model results are achieved by simulating pre-exposure with f ¼ 0.6 and haloperidol with y ¼ À0.2.…”

Section: Discussionmentioning

confidence: 99%

“…In two pivotal studies, Solomon et al (1981) and Weiner et al (1981) both reported the disruption of LI (failure of pre-exposure to retard subsequent conditioning) in animals treated with amphetamine (a dopamine-enhancing agent). Links with the pharmacology of psychosis are reinforced by findings that APDs reverse the amphetamine-induced LI deficit in animals (reviewed in Moser et al, 2000) and enhance the standard LI effect in normal animals (Weiner et al, 1987). Based on this pharmacological connection, LI-disruption was suggested as a potential model of the selective attention deficit found in schizophrenia.…”

Section: Generalizing the Model To LI Disruption Introductionmentioning

confidence: 99%

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Linking Animal Models of Psychosis to Computational Models of Dopamine Function

Smith

Becker

et al. 2006

Neuropsychopharmacol

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Psychosis is linked to dysregulation of the neuromodulator dopamine and antipsychotic drugs (APDs) work by blocking dopamine receptors. Dopamine-modulated disruption of latent inhibition (LI) and conditioned avoidance response (CAR) have served as standard animal models of psychosis and antipsychotic action, respectively. Meanwhile, the 'temporal difference' algorithm (TD) has emerged as the leading computational model of dopamine neuron firing. In this report TD is extended to include action at the level of dopamine receptors in order to explain a number of behavioral phenomena including the dose-dependent disruption of CAR by APDs, the temporal dissociation of the effects of APDs on receptors vs behavior, the facilitation of LI by APDs, and the disruption of LI by amphetamine. The model also predicts an APD-induced change to the latency profile of CARFa novel prediction that is verified experimentally. The model's primary contribution is to link dopamine neuron firing, receptor manipulation, and behavior within a common formal framework that may offer insights into clinical observations. Neuropsychopharmacology Keywords: dopamine; temporal difference learning; psychosis; conditioned avoidance; latent inhibition; computational modeling INTRODUCTIONPerturbations in dopamine transmission are central to a number of human illnesses including addiction, Parkinson's disease, attention-deficit hyperactivity disorder (ADHD), and schizophrenia. As a result there has been tremendous interest in understanding the psychological and behavioral functions of dopamine, and a number of overlapping hypotheses have been suggested. These hypotheses include roles for dopamine in hedonia (Wise, 1982), reward learning (Robbins and Everitt, 1996), incentive salience (Berridge and Robinson, 1998), sensorimotor function and anergia (Salamone et al, 1994). In parallel, mathematical models have been used to link some of these psychological constructs to the physiology of the dopamine system (Schultz, 1998;Seamans and Yang, 2004). Many of these models have concentrated on 'normal' dopaminergic conditions (McClure et al, 2003;Schultz et al, 1997), and the current aim is to explore how one such model can be extended to address the abnormal conditions encountered in schizophrenia and their treatment.Of all the mathematical models linking dopamine, behavior, and psychology, the Temporal Difference Learning model (TD) has enjoyed particular success (Montague et al, 1996;Redish, 2004;Schultz et al, 1997). TD is a powerful formal reinforcement learning technique that has been used to solve many challenging machine learning problems. For example, the technique has been used to train computers to play backgammon to the highest human standards by associating a simulated reward with winning a game (Tesauro, 1994). At the heart of TD is a predictionerror signal that is zero if the environment behaves as expected, positive in response to unexpected reward, and negative following omission of expected reward. Striking parallels have been observed between...

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Section: Resultsmentioning

confidence: 92%

Section: Discussionmentioning

confidence: 99%

Section: Generalizing the Model To LI Disruption Introductionmentioning

confidence: 99%

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Linking Animal Models of Psychosis to Computational Models of Dopamine Function

Smith

Becker

et al. 2006

Neuropsychopharmacol

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“…A second relevant difference between CTA and other procedures used to reproduce the LI effect is the number of experimental stages involved. Some non-CTA LI procedures use a preexposure stage and a conditioning stage that also serves as a test for conditioning (e.g., McLaren et al, 1994;Weiner, Feldon & Katz, 1987). Obviously, context changes between phases in a 3-stage procedure allow for many more combinations as compared to procedures which include only two stages.…”

Section: Effects Of Context On Latent Inhibitionmentioning

confidence: 99%

Disentangling the effects of context change and context familiarity on Latent Inhibition with a Conditioned Taste Aversion procedure

Casa

Mena

Orgaz

et al. 2013

Learning and Motivation

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“…The doses of scopolamine were chosen based on studies showing that they did not disrupt tone-shock conditioning (Anagnostaras et al, 1999). The doses of haloperidol, clozapine, and amphetamine were chosen based on our previous LI studies using these drugs (Weiner et al, 1987(Weiner et al, , 1996. The doses of physostigmine were chosen based on previous behavioral experiments with this drug (Jones and Shannon, 2000b;Shannon and Peters, 1990).…”

Section: Drugsmentioning

confidence: 99%

Scopolamine Induces Disruption of Latent Inhibition which is Prevented by Antipsychotic Drugs and an Acetylcholinesterase Inhibitor

Barak

Weiner

2006

Neuropsychopharmacol

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The fact that muscarinic antagonists may evoke a psychotic state ('antimuscarinic psychosis'), along with findings of cholinergic alterations in schizophrenia, have kindled an interest in the involvement of the cholinergic system in this disorder. Latent inhibition (LI) is a crossspecies phenomenon manifested as a poorer conditioning of a stimulus seen when the stage of conditioning is preceded by a stage of repeated nonreinforced pre-exposure to that stimulus, and is considered to index the capacity to ignore irrelevant stimuli. Amphetamine-induced LI disruption and its reversal by antipsychotic drugs (APDs) is a well-established model of positive symptoms of schizophrenia. Here, we tested whether the muscarinic antagonist scopolamine would disrupt LI and whether such disruption would be reversed by APDs and by the acetylcholinesterase inhibitor physostigmine. The results showed that scopolamine at doses of 0.15 and 0.5 mg/kg disrupted LI, and that this effect was due to the action of the drug in the pre-exposure stage, suggesting a role of muscarinic transmission in attentional processes underlying LI. Both the typical and the atypical APDs, haloperidol and clozapine, reversed scopolamine-induced LI disruption when given in conditioning or in both stages, but not in pre-exposure, indicating that the mechanism of antipsychotic action in this model is independent of the mechanism of action of the propsychotic drug. Scopolamine-induced LI disruption was reversed by physostigmine (0.05 and 0.15 mg/kg), which was ineffective in reversing amphetamine-induced LI disruption, pointing to distinct mechanisms underlying LI disruption by these two propsychotic drugs. The latter was further supported by the finding that unlike amphetamine, the LI-disrupting doses of scopolamine did not affect activity levels. We propose scopolamine-induced LI disruption as a model of cholinergic-related positive symptoms in schizophrenia. Neuropsychopharmacology (2007) 32, 989-999.

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Facilitation of the expression but not the acquisition of latent inhibition by haloperidol in rats

Cited by 134 publications

References 34 publications

Linking Animal Models of Psychosis to Computational Models of Dopamine Function

Linking Animal Models of Psychosis to Computational Models of Dopamine Function

Disentangling the effects of context change and context familiarity on Latent Inhibition with a Conditioned Taste Aversion procedure

Scopolamine Induces Disruption of Latent Inhibition which is Prevented by Antipsychotic Drugs and an Acetylcholinesterase Inhibitor

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