Effects of diazepam, pentobarbital, scopolamine and the timing of saline injection on learned immobility in rats
Abstract
The rat forced-swimming test (FST) is widely used for screening substances with a potential antidepressant effect. Rat immobility shown in the FST has been interpreted as "behavioral despair" and has been suggested as an animal model of human depression. In the following series of experiments, it is shown that pentobarbital and scopolamine administered immediately after the first phase, and diazepam administered 15 minutes before the first phase, behave as false positives in the FST. It is concluded that the learning-memory hypothesis seems to cope better with the behavior of rats during the FST than the "behavioral despair" hypothesis. It is also shown that the sensitivity of the FST is affected by the fact that the last saline injection, one hour before the second phase, increases the animals' mobility.
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Antagonism of mAChRs or nAChRs, or blockade of ACh signaling through nAChRs with partial agonists, can decrease depression-like behavior in rodents.
“Consistent with an increase in ACh leading to symptoms of depression, antagonism of mAChRs or nAChRs, or blockade of ACh signaling through nAChRs with partial agonists, can decrease depression-like behavior in rodents (Caldarone et al., 2004; De Pablo et al., 1991; Mineur et al., 2007; Picciotto et al., 2002; Rabenstein et al., 2006).”
From Acetylcholine as a Neuromodulator: Cholinergic Signaling Shapes Nervous System Function and Behavior (2012) · cites this paper as De Pablo et al., 1991
Cites
Helplessness: On Depression, Development, and Death
Seligman, M. E. P. (1975) · CERN Document Server (European Organization for Nuclear Research) · Cited by 6,181 · see citing works
Depression: a new animal model sensitive to antidepressant treatments
PORSOLT, R. D., LE PICHON, M., & JALFRE, M. (1977) · Nature · doi:10.1038/266730a0 · Cited by 4,451 · see citing works
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 · see citing works
Psychopharmacology: The third generation of progress
O’Connell, R. A. (1988) · Comprehensive Psychiatry · doi:10.1016/0010-440x(88)90057-0 · Cited by 3,020 · see citing works
Protein synthesis and memory: A review.
Davis, H. P., & Squire, L. R. (1984) · Psychological Bulletin · doi:10.1037/0033-2909.96.3.518 · Cited by 1,505 · see citing works
Psychopathology : experimental models
Maser, J. D., & Seligman, M. E. P. (1977) · W.H. Freeman eBooks · Cited by 487 · see citing works
Sleep states and learning: A review of the animal literature
Smith, C. (1985) · Neuroscience & Biobehavioral Reviews · doi:10.1016/0149-7634(85)90042-9 · Cited by 298 · see citing works
The Physiological Basis of Memory
Hogarth, P. J. (1983) · Elsevier eBooks · doi:10.1016/b978-0-12-213460-9.x5001-1 · Cited by 243 · see citing works
Learned immobility explains the behavior of rats in the forced swimming test
Pablo, J. M. D., Parra, A., Segovia, S., & Guillamón, A. (1989) · Physiology & Behavior · doi:10.1016/0031-9384(89)90261-8 · Cited by 172 · see citing works
Self-citationAntidepressants: Neurochemical, Behavioral and Clinical Perspectives
Jenner, P. M. (1982) · Journal of Neurology Neurosurgery & Psychiatry · doi:10.1136/jnnp.45.6.574-b · Cited by 164 · see citing works
Effects of antidepressants in the rat forced swimming test
Kitada, Y., Miyauchi, T., Satoh, A., & Satoh, S. (1981) · European Journal of Pharmacology · doi:10.1016/0014-2999(81)90269-7 · Cited by 159 · see citing works
Chronic restraint stress elicits a positive antidepressant response on the forced swim test
Platt, J., & Stone, E. A. (1982) · European Journal of Pharmacology · doi:10.1016/0014-2999(82)90508-8 · Cited by 123 · see citing works
Glucocorticoids facilitate the retention of acquired immobility during forced swimming
Veldhuis, H. D., Korte, C. C. M. M. D., & de Kloet, E. R. (1985) · European Journal of Pharmacology · doi:10.1016/0014-2999(85)90693-4 · Cited by 103 · see citing works
Effects of benzodiazepines on acquisition and performance: A critical assessment
Cole, S. O. (1986) · Neuroscience & Biobehavioral Reviews · doi:10.1016/0149-7634(86)90013-8 · Cited by 87 · see citing works
Duncan, G. E., Breese, G. R., Criswell, H. E., Stumpf, W. E., Mueller, R. A., & Covey, J. B. (1986) · Journal of Pharmacology and Experimental Therapeutics · doi:10.1016/s0022-3565(25)24935-7 · Cited by 68 · see citing works
Diazepam and human memory: Influence on acquisition, retrieval, and state-dependent learning
Petersen, R. C., & Ghoneim, M. M. (1980) · Progress in Neuro-Psychopharmacology · doi:10.1016/0364-7722(80)90064-8 · Cited by 57 · see citing works
Effect of GABAergic drugs in the behavioral ‘despair’ test in rats
Borsini, F., Evangelista, S., & Meli, A. (1986) · European Journal of Pharmacology · doi:10.1016/0014-2999(86)90498-x · Cited by 48 · see citing works
Effects of two antidepressants on memory performance in depressed outpatients: a double-blind study
Lamping, D. L., Spring, B. J., & Gelenberg, A. J. (1984) · Psychopharmacology · doi:10.1007/bf00427455 · Cited by 39 · see citing works
FACILITATION OF MEMORY CONSOLIDATION
Martinez, J. L., Jensen, R. A., & McGaugh, J. L. (1983) · Elsevier eBooks · doi:10.1016/b978-0-12-213460-9.50008-3 · Cited by 32 · see citing works
Effects of repeated doses of fluvoxamine, mianserin and placebo on memory and measures of sedation
Curran, H. V., Shine, P. J., & LADER, M. H. (1986) · Psychopharmacology · doi:10.1007/bf00174375 · Cited by 31 · see citing works
Emotionality and REMD: A rat swimming model
Hawkins, J., Phillips, N., Moore, J. D., Gilliland, M. A., Dunbar, S., & Hicks, R. A. (1980) · Physiology & Behavior · doi:10.1016/0031-9384(80)90202-4 · Cited by 30 · see citing works
The effect of diazepam and of agents which change gabaergic functions in immobility in mice
Nagatani, T., Sugihara, T., & Kodaira, R. (1984) · European Journal of Pharmacology · doi:10.1016/0014-2999(84)90459-x · Cited by 30 · see citing works
Nagatani, T., Yamamoto, T., Sugihara, T., & Ueki, S. (1987) · European Journal of Pharmacology · doi:10.1016/0014-2999(87)90648-0 · Cited by 29 · see citing works
van Luijtelaar, E. L. J. M., & Coenen, A. M. L. (1985) · SLEEP · doi:10.1093/sleep/8.1.49 · Cited by 27 · see citing works
Sodium valporate reduces immobility in the behavioral ‘depair’ test in rats
Truel, A. F., Escolan, F. B., Escorihuela, R. M., Yáñez, P., & Tobeña, A. (1988) · European Journal of Pharmacology · doi:10.1016/0014-2999(88)90829-1 · Cited by 23 · see citing works
Lucki, I., & Nobler, M. S. (1985) · Pharmacology Biochemistry and Behavior · doi:10.1016/0091-3057(85)90388-0 · Cited by 21 · see citing works
ELECTROCONVULSIVE SHOCK AND MEMORY
Schneider, A. M., & PLOUGH, M. (1983) · Elsevier eBooks · doi:10.1016/b978-0-12-213460-9.50014-9 · Cited by 19 · see citing works
Swimming immobility of REM sleep deprived rats reared in different environments
Hodgson, J. A. (1984) · Physiology & Behavior · doi:10.1016/0031-9384(84)90063-5 · Cited by 18 · see citing works
Effects of psychotropic drugs on cognition and memory in normal humans and animals
Judd, L. L., Squire, L. R., Butters, N., Salmon, D. P., & Paller, K. A. (1987) · Cited by 12 · see citing works
Tricyclic and Monoamine-Oxidase-Inhibitor Antidepressants: Clinical Use
Kupfer, D. J., & DETRE, T. P. (1987) · Springer eBooks · doi:10.1007/978-1-4613-4045-4_5 · Cited by 11 · see citing works
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1 of the 31 references couldn’t be matched to a known paper.
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Acetylcholine as a Neuromodulator: Cholinergic Signaling Shapes Nervous System Function and Behavior
Picciotto, M. R., Higley, M. J., & Mineur, Y. S. (2012) · Neuron · doi:10.1016/j.neuron.2012.08.036 · Cited by 1,404 · see citing works
Factors influencing behavior in the forced swim test
Bogdanova, O. V., Kanekar, S., D’Anci, K. E., & Renshaw, P. F. (2013) · Physiology & Behavior · doi:10.1016/j.physbeh.2013.05.012 · Cited by 465 · see citing works
Coping with the Forced Swim Stressor: Towards Understanding an Adaptive Mechanism
de Kloet, E. R., & Molendijk, M. L. (2016) · Neural Plasticity · doi:10.1155/2016/6503162 · Cited by 353 · see citing works
Acute and chronic antidepressant drug treatment in the rat forced swimming test model of depression.
Detke, M. J., Johnson, J. E., & Lucki, I. (1997) · Experimental and Clinical Psychopharmacology · doi:10.1037/1064-1297.5.2.107 · Cited by 318 · see citing works
Identifying fast-onset antidepressants using rodent models
Ramaker, M. J., & Dulawa, S. C. (2017) · Molecular Psychiatry · doi:10.1038/mp.2017.36 · Cited by 181 · see citing works
Armario, A. (2021) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2021.06.014 · Cited by 180 · see citing works
New perspectives on the basal forebrain cholinergic system in Alzheimer’s disease
Berry, A. S., & Harrison, T. M. (2023) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2023.105192 · Cited by 97 · see citing works
Bekku, N., & Yoshimura, H. (2005) · Psychopharmacology · doi:10.1007/s00213-005-0179-0 · Cited by 89 · see citing works
Ahmadalipour, A., Sadeghzadeh, J., Vafaei, A. A., Bandegi, A. R., Mohammadkhani, R., & Rashidy‐Pour, A. (2015) · Neuroscience · doi:10.1016/j.neuroscience.2015.08.015 · Cited by 71 · see citing works
Estrogens participate in the antidepressant-like effect of desipramine and fluoxetine in male rats
Martı́nez-Mota, L., Cruz-Martínez, J. E., Márquez-Baltazar, S., & Fernández‐Guasti, A. (2007) · Pharmacology Biochemistry and Behavior · doi:10.1016/j.pbb.2007.09.003 · Cited by 61 · see citing works
Ethopharmacology of the Antidepressant Effect of Clonazepam in Diabetic Rats
Gomez, R., & Barros, H. M. T. (2000) · Pharmacology Biochemistry and Behavior · doi:10.1016/s0091-3057(00)00221-5 · Cited by 52 · see citing works
Ramos‐Ortolaza, D. L., Doreste-Méndez, R., Alvarado-Torres, J. K., & Torres-Reverón, A. (2017) · Behavioural Brain Research · doi:10.1016/j.bbr.2017.04.016 · Cited by 42 · see citing works
Antidepressant-like effects of glucagon-like peptide-2 in mice occur via monoamine pathways
Iwai, T., Hayashi, Y., Narita, S., Kasuya, Y., Jin, K., Tsugane, M., & Oka, J. (2009) · Behavioural Brain Research · doi:10.1016/j.bbr.2009.06.020 · Cited by 39 · see citing works
Laino, C. H., Fonseca, C., Sterin-Speziale, N. B., Slobodianik, N., & Reinés, A. G. (2010) · European Journal of Pharmacology · doi:10.1016/j.ejphar.2010.08.047 · Cited by 35 · see citing works
Effect of α2-adrenergic drugs on REM sleep deprivation-induced increase in swimming activity
Asakura, W., Matsumoto, K., Ohta, H., & Watanabe, H. (1993) · Pharmacology Biochemistry and Behavior · doi:10.1016/0091-3057(93)90325-n · Cited by 33 · see citing works
Antidepressants and the resilience to early-life stress in inbred mouse strains
Binder, E., Malki, K., Paya-Cano, J. L., Fernandes, C., Aitchison, K. J., Mathé, A. A., Sluyter, F., & Schalkwyk, L. C. (2011) · Pharmacogenetics and Genomics · doi:10.1097/fpc.0b013e32834b3f35 · Cited by 32 · see citing works
Carpenter, J. M., Jourdan, M. K., Fountain, E. M., Ali, Z., Abe, N., Khan, I. A., & Sufka, K. J. (2016) · Journal of Ethnopharmacology · doi:10.1016/j.jep.2016.08.019 · Cited by 28 · see citing works
Ahmadalipour, A., & Rashidy‐Pour, A. (2014) · Physiology & Behavior · doi:10.1016/j.physbeh.2014.10.038 · Cited by 25 · see citing works
Learned immobility is also involved in the forced swimming test in mice
Parra, A., Vinader‐Caerols, C., Monleón, S., & Simón, V. M. (1999) · Cited by 25 · see citing works
Sun, Y., Evans, J., Russell, B., Kydd, R. R., & Connor, B. J. (2013) · Neuropharmacology · doi:10.1016/j.neuropharm.2013.04.021 · Cited by 24 · see citing works
Su, J., Hato-Yamada, N., Araki, H., & Yoshimura, H. (2013) · Journal of Pharmacological Sciences · doi:10.1254/jphs.13145fp · Cited by 21 · see citing works
Neoechinulin A induced memory improvements and antidepressant-like effects in mice
Sasaki‐Hamada, S., Hoshi, M., Niwa, Y., Ueda, Y., Kokaji, A., Kamisuki, S., Kuramochi, K., Sugawara, F., & Oka, J. (2016) · Progress in Neuro-Psychopharmacology and Biological Psychiatry · doi:10.1016/j.pnpbp.2016.08.002 · Cited by 21 · see citing works
Animal Models to Detect Antidepressants
Willner, P., & Papp, M. (1997) · Humana Press eBooks · doi:10.1007/978-1-59259-474-0_12 · Cited by 21 · see citing works
Chompré, G., Sambolin‐Escobales, L., Cruz, M. L., Sanchez, R., Rodriguez, Y., Rodríguez-Santiago, R. E., Yamamura, Y., & Appleyard, C. B. (2022) · Heliyon · doi:10.1016/j.heliyon.2022.e11194 · Cited by 18 · see citing works
Maternal fluoxetine treatment decreases behavioral response to dopaminergic drugs in female pups
Favaro, P. D. N., Costa, L. C., & Moreira, E. G. (2008) · Neurotoxicology and Teratology · doi:10.1016/j.ntt.2008.05.002 · Cited by 17 · see citing works
Involvement of muscarinic receptor mechanisms in antidepressant drug action
Witkin, J. M., Smith, J. L., Golani, L. K., Brooks, E. A., & Martin, A. E. (2020) · Advances in pharmacology · doi:10.1016/bs.apha.2020.03.003 · Cited by 16 · see citing works
Huzián, O., Baka, J., Csakvari, E., Dobos, N., Leranth, C., Siklós, L., Duman, R. S., Farkas, T., & Hajszán, T. (2021) · Neuroscience · doi:10.1016/j.neuroscience.2021.01.029 · Cited by 14 · see citing works
Yoo, H. (2000) · Physiology & Behavior · doi:10.1016/s0031-9384(00)00261-4 · Cited by 14 · see citing works
Enginar, N., Yamantürk-Çelik, P., Nurten, A., & Güney, D. B. (2016) · Naunyn-Schmiedeberg s Archives of Pharmacology · doi:10.1007/s00210-016-1236-4 · Cited by 11 · see citing works
Role of corticotropin-releasing factor in forced swimming test
Garcı́a-Lecumberri, C., & Ambrosio, E. (1998) · European Journal of Pharmacology · doi:10.1016/s0014-2999(97)01515-x · Cited by 11 · see citing works
Malikowska‐Racia, N., Koniewski, M., Gołębiowska, J., & Popik, P. (2023) · Journal of Psychopharmacology · doi:10.1177/02698811231205692 · Cited by 6 · see citing works
Food restriction does not relieve PTSD-like anxiety
Hendriksen, H., Bink, D. I., Vergoossen, D. L. E., van Slobbe, E. S., Olivier, B., & Oosting, R. S. (2014) · European Journal of Pharmacology · doi:10.1016/j.ejphar.2014.10.060 · Cited by 5 · see citing works
Vlasov, I. N., Filatova, E. V., Slominsky, P. A., & Shadrina, M. I. (2023) · Scientific Reports · doi:10.1038/s41598-023-36611-5 · Cited by 4 · see citing works
From non-pharmacological interventions to therapeutic targets for the treatment of PTSD
Hendriksen, H. M. A. (2012) · Utrecht University Repository (Utrecht University) · Cited by 2 · see citing works
The link between learning performance, immobility in the forced swim test, and hippocampal glia
Ozcan, T. S., Sara, Y., Arıkan, K. B., Ünal, B., & Ünal, Ç. T. (2022) · Experimental Biomedical Research · doi:10.30714/j-ebr.2022173848
- Authors
- De Pablo, J. M., Ortiz-Caro, J., Sanchez-Santed, F., & Guillamón, A.
- Affiliations
- Universidad Nacional de Educación a Distancia (ES)
- Corresponding author
- Guillamón, Antonio
- ORCID
- Guillamón, Antonio
- Venue
- Physiology & Behavior
- Publisher
- Elsevier BV
- Published
- 1991-11
- Volume
- 50
- Issue
- 5
- Pages
- 895-899
- ISSN
- 0031-9384 (ISSN-L)
- OpenAlex
- W2087698327
- Cited by
- 35
- References
- 31
- Citations by year
- 2023: 3 · 2022: 2 · 2021: 2 · 2020: 1 · 2017: 2 · 2016: 4 · 2015: 1 · 2014: 2 · 2013: 3 · 2012: 2
- FWCI
- 0.42
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Physiology & Behavior (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Pharmacology › Treatment of Major Depression
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
- Keywords
- forced swim test, immobility, diazepam, pentobarbital, scopolamine, false positives, antidepressant screening, behavioral despair, depression model, rats
- MeSH terms
- Animals, Diazepam, Dose-Response Relationship, Drug, Escape Reaction, Helplessness, Learned, Male, Motor Activity, Pentobarbital, Rats, Inbred Strains, Mental Recall, Scopolamine, Swimming, Rats
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