The DOI matches its Crossref record; 164 of the 167 references it cites were found in a registry or an index.
Removing Obstacles in Neuroscience Drug Discovery: The Future Path for Animal Models
Open accessAbstract
Despite great advances in basic neuroscience knowledge, the improved understanding of brain functioning has not yet led to the introduction of truly novel pharmacological approaches to the treatment of central nervous system (CNS) disorders. This situation has been partly attributed to the difficulty of predicting efficacy in patients based on results from preclinical studies. To address these issues, this review critically discusses the traditional role of animal models in drug discovery, the difficulties encountered, and the reasons why this approach has led to suboptimal utilization of the information animal models provide. The discussion focuses on how animal models can contribute most effectively to translational medicine and drug discovery and the changes needed to increase the probability of achieving clinical benefit. Emphasis is placed on the need to improve the flow of information from the clinical/human domain to the preclinical domain and the benefits of using truly translational measures in both preclinical and clinical testing. Few would dispute the need to move away from the concept of modeling CNS diseases in their entirety using animals. However, the current emphasis on specific dimensions of psychopathology that can be objectively assessed in both clinical populations and animal models has not yet provided concrete examples of successful preclinical-clinical translation in CNS drug discovery. The purpose of this review is to strongly encourage ever more intensive clinical and preclinical interactions to ensure that basic science knowledge gained from improved animal models with good predictive and construct validity readily becomes available to the pharmaceutical industry and clinical researchers to benefit patients as quickly as possible.
Overview
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
In the citing paper
“conservation and divergence in brain function between humans and other species provide essential information for the understanding of drug action, which is often poorly conserved across species6.”
From An anatomically comprehensive atlas of the adult human brain transcriptome (2012) · cites this paper as [6]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cites
Construct validity in psychological tests.
Cronbach, L. J., & Meehl, P. E. (1955) · Psychological Bulletin · doi:10.1037/h0040957 · Cited by 11,195
Can the pharmaceutical industry reduce attrition rates?
Kola, I., & Landis, J. (2004) · Nature Reviews Drug Discovery · doi:10.1038/nrd1470 · Cited by 4,167
THE CATECHOLAMINE HYPOTHESIS OF AFFECTIVE DISORDERS: A REVIEW OF SUPPORTING EVIDENCE
Schildkraut, J. J. (1965) · American Journal of Psychiatry · doi:10.1176/ajp.122.5.509 · Cited by 3,568
SELECTIVE LOSS OF CENTRAL CHOLINERGIC NEURONS IN ALZHEIMER'S DISEASE
DAVIES, P. (1976) · The Lancet · doi:10.1016/s0140-6736(76)91936-x · Cited by 3,565
Krystal, J. H. (1994) · Archives of General Psychiatry · doi:10.1001/archpsyc.1994.03950030035004 · Cited by 3,330
Hopkins, A. L., & Groom, C. R. (2002) · Nature Reviews Drug Discovery · doi:10.1038/nrd892 · Cited by 3,305
Behavioural despair in rats: A new model sensitive to antidepressant treatments
Porsolt, R. D., Anton, G., Blavet, N., & Jalfre, M. (1978) · European Journal of Pharmacology · doi:10.1016/0014-2999(78)90118-8 · Cited by 3,138
International Union of Pharmacology classification of receptors for 5-hydroxytryptamine (Serotonin).
Hoyer, D., Clarke, D. E., Fozard, J. R., Hartig, P. R., Martin, G. R., Mylecharane, E. J., Saxena, P. R., & Humphrey, P. P. A. (1994) · Pharmacological Reviews · doi:10.1016/s0031-6997(25)06783-3 · Cited by 3,025
Psychopharmacology: The Fourth Generation of Progress
Bloom, F. E., & Kupfer, D. J. (1995) · Medical Entomology and Zoology · Cited by 2,985
Recent advances in the phencyclidine model of schizophrenia
(1991) · American Journal of Psychiatry · doi:10.1176/ajp.148.10.1301 · Cited by 2,904
Research works printed but not linked: 3
- Bilder RM, Lieberman JA, Kim Y, Alvir JM, Reiter G (1992). Methylphenidate and neuroleptic effects on oral word production in schizophrenia. Neuropsychiatry Neuropsychol Behav Neurol 5: 262–271.
- Horowski R, Sastre-y-Hernandez M (1985). Clinical effects of neurotropic selective cAMP phosphodiesterase inhibitor rolipram in depressed patients: global evaluation of the preliminary reports. Curr Ther Res 38: 23–29.
- Murray Law B (2007). What's ahead for rimonabant?. Doc News 4: 10–13.
Cited by
Sorted by citations
An anatomically comprehensive atlas of the adult human brain transcriptome
Hawrylycz, M. J., Lein, E. S., Guillozet-Bongaarts, A. L., Shen, E. H., Ng, L., Miller, J. A., van de Lagemaat, L. N., Smith, K. A., Ebbert, A., Riley, Z. L., et al. (2012) · Nature · doi:10.1038/nature11405 · Cited by 3,083
Animal models of neuropsychiatric disorders
Nestler, E. J., & Hyman, S. E. (2010) · Nature Neuroscience · doi:10.1038/nn.2647 · Cited by 2,023
Conserved cell types with divergent features in human versus mouse cortex
Hodge, R. D., Bakken, T. E., Miller, J. A., Smith, K. A., Barkan, E. R., Graybuck, L. T., Close, J. L., Long, B., Johansen, N., Penn, O., et al. (2019) · Nature · doi:10.1038/s41586-019-1506-7 · Cited by 1,775
Millan, M. J., Agid, Y., Brüne, M., Bullmore, E. T., Carter, C. S., Clayton, N. S., Connor, R., Davis, S., Deakin, B., DeRubeis, R. J., et al. (2012) · Nature Reviews Drug Discovery · doi:10.1038/nrd3628 · Cited by 1,292
Self-citationThe neurobiology of anhedonia and other reward-related deficits
Der-Avakian, A., & Markou, A. (2012) · Trends in Neurosciences · doi:10.1016/j.tins.2011.11.005 · Cited by 1,130
Self-citation
Metadata
- Authors
- Markou, A., Chiamulera, C., Geyer, M. A., Tricklebank, M., & Steckler, T.
- Affiliations
- University of California San Diego (US)
- Eli Lilly (United Kingdom) (GB)
- Corresponding author
- Markou, Athina
- Venue
- Neuropsychopharmacology
- Published
- 2008-10-01
- Volume
- 34
- Issue
- 1
- Pages
- 74-89
- ISSN
- 0893-133X (ISSN-L)
- 1740-634X
- PMC
- PMC2651739
- OpenAlex
- W2142885788
- Cited by
- 328
- References
- 167
- Citations by year
- 2026: 6 · 2025: 14 · 2024: 10 · 2023: 8 · 2022: 8 · 2021: 14 · 2020: 12 · 2019: 14 · 2018: 18 · 2017: 16 · 2016: 15 · 2015: 30 · 2014: 28 · 2013: 27 · 2012: 35
- FWCI
- 6.32
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Neuropsychopharmacology (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- U.S. Department of Veterans Affairs
- Tobacco-Related Disease Research Program
- National Institutes of Health
- National Institute of Mental Health (U01 MH 69062, 5R01MH52885, R01MH071916, U01MH069062, R01MH052885, R01MH062527)
- National Institute on Drug Abuse (R01DA023926, R56DA011946, R01DA002925, 2R01DA11946, R01DA023209, 5R01 DA02925, R01DA011946)
- NIH Clinical Center
- Topics
- Health Sciences › Veterinary › Small Animals › Animal testing and alternatives
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Neuroscience › Cognitive Neuroscience › Memory and Neural Mechanisms
- Keywords
- animal models, CNS drug discovery, translational medicine, predictive validity, construct validity, central nervous system disorders, psychopathology, clinical trials, preclinical drug testing
- MeSH terms
- Animals, Central Nervous System Diseases, Clinical Trials as Topic, Disease Models, Animal, Drug Evaluation, Preclinical, Forecasting, Humans, Neurosciences, Reproducibility of Results, Models, Animal, Biomarkers, Pharmacological, Drug Discovery
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
