Preclinical Behavioral Models for Predicting Antipsychotic Activity

Castagné, Vincent; Moser, Paul C.; Porsolt, Roger D.

doi:10.1016/s1054-3589(08)57010-4

Cited by 64Schizophrenia research and treatmentNeurotransmitter Receptor Influence on BehaviorNeuroscience and Neuropharmacology Research

Preclinical Behavioral Models for Predicting Antipsychotic Activity

Castagné, Vincent, Moser, Paul C., Porsolt, Roger D.·2009·Advances in Pharmacology

DOI 10.1016/s1054-3589(08)57010-4

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Abstract

Schizophrenia is a major psychiatric disease that is characterized by three distinct symptom domains: positive symptoms, negative symptoms, and cognitive impairment. Additionally, treatment with classical antipsychotic medication can be accompanied by important side effects that involve extrapyramidal symptoms (EPS). The discovery of clozapine in the 1970s, which is efficacious in all three symptom domains and has a reduced propensity to induce EPS, has driven research for new antipsychotic agents with a wider spectrum of activity and a lower propensity to induce EPS. The following chapter reviews existing behavioral procedures in animals for their ability to predict compound efficacy against schizophrenia symptoms and liability to induce EPS. Rodent models of positive symptoms include procedures related to hyperfunction in central dopamine and serotonin (5-hydroxytryptamine) systems and hypofunction of central glutamatergic (N-methyl-d-aspartate) neurotransmission. Procedures for evaluating negative symptoms include rodent models of anhedonia, affective flattening, and diminished social interaction. Cognitive deficits can be assessed in rodent models of attention (prepulse inhibition (PPI), latent inhibition) and of learning and memory (passive avoidance, object and social recognition, Morris water maze, and operant-delayed alternation). The relevance of the conditioned avoidance response (CAR) is also discussed. A final section reviews animal procedures for assessing EPS liability, in particular parkinsonism (catalepsy), acute dystonia (purposeless chewing in rodents, dystonia in monkeys), akathisia (defecation in rodents), and tardive dyskinesia (long-term antipsychotic treatment in rodents and monkeys).

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Amylin: Pharmacology, Physiology, and Clinical Potential
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Authors: Castagné, V., Moser, P. C., & Porsolt, R. D.
Affiliations: Porsolt (France) (FR)
ORCID: Castagné, Vincent
Moser, Paul C.
Venue: Advances in Pharmacology
Publisher: Elsevier
Published: 2009
Volume: 57
Pages: 381-418
ISSN: 1054-3589 (ISSN-L)
DOI: 10.1016/s1054-3589(08)57010-4
OpenAlex: W1512804011
Cited by: 64
References: 179
Citations by year: 2026: 1 · 2025: 1 · 2024: 1 · 2023: 1 · 2022: 6 · 2021: 2 · 2020: 2 · 2019: 3 · 2018: 3 · 2017: 3 · 2016: 1 · 2015: 3 · 2014: 5 · 2013: 10 · 2012: 12
FWCI: 35.98
Type: book chapter
Language: en
Open access: closed
Locations: Advances in pharmacology (publishedVersion)
PubMed (publishedVersion)
Topics: Health Sciences › Medicine › Psychiatry and Mental health › Schizophrenia research and treatment
Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
Keywords: schizophrenia, antipsychotic drug discovery, positive symptoms, negative symptoms, cognitive impairment, extrapyramidal symptoms, clozapine, prepulse inhibition, latent inhibition, anhedonia, social recognition, conditioned avoidance response, parkinsonism, acute dystonia, akathisia, tardive dyskinesia, NMDA receptor hypofunction
MeSH terms: Animals, Behavior, Animal, Cognition, Disease Models, Animal, Drug Evaluation, Preclinical, Humans, Antipsychotic Agents

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Preclinical Behavioral Models for Predicting Antipsychotic Activity

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