Genetic deletion and pharmacological blockade of CB1 receptors modulates anxiety in the shock‐probe burying test
Abstract
Cannabinoids affect various behavioral processes, including emotion, learning and memory, which may bspecifically regulated through the CB1 receptors. The exact role CB1 receptors play in anxiety remains unclear. Both genetic and pharmacological blockade of CB1 receptors have produced inconsistent effects on anxiety. However, these studies examined passive avoidance as an index of anxiety. In the present study, both active and passive avoidance were examined using the shock‐probe burying test while CB1 receptors were blocked genetically or pharmacologically. In the shock‐probe burying test, anxiety is reflected by increased burying (increased active avoidance) and increased freezing (increased passive avoidance). In addition, probe‐contacts may reflect cognitive performance and/or passive avoidance. As there have been few studies examining mouse behavior in the shock‐probe burying test, experiment 1 was designed to pharmacologically validate this model in mice. Our results indicated that administration (i.p.) of chlordiazepoxide (4 mg/kg) or FG7412 (5 mg/kg) decreased and increased burying behavior, respectively, without affecting freezing or the number of probe contacts. Experiments 2 and 3 showed that both CB1 knockout mice and mice injected (i.p.) with 3 or 10 mg/kg, but not 1 mg/kg, of the CB1 receptor antagonist SR141716A had lower burying scores, fewer contacts with the probe and similar freezing times compared with wild‐type mice and mice injected with vehicle (experiments 2 and 3). Collectively, these results suggest that CB1 receptor blockade reduces some, but not all, aspects of anxiety. The decrease in probe contacts induced by CB1 receptor blockade may be due to enhanced cognition.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
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?
Rodents will bury an electrified probe after having received shocks from the probe and will spontaneously bury marbles introduced as a novelty into their home cages.
“Rodents will bury an electrified probe after having received shocks from the probe43 and will even spontaneously bury marbles introduced as a novelty into their home cages44.”
From Resolving the neural circuits of anxiety (2015) · cites this paper as [43]
Cites
Isolation and Structure of a Brain Constituent That Binds to the Cannabinoid Receptor
Devane, W. A., Hanuš, L., Breuer, A., Pertwee, R. G., Stevenson, L. A., Griffin, G., Gibson, D., Mandelbaum, A., Etinger, A., & Mechoulam, R. (1992) · Science · doi:10.1126/science.1470919 · Cited by 5,633 · see citing works
Ledent, C. A., Valverde, O., Cossu, G., Petitet, F., Aubert, J.-F., Beslot, F., Böhme, G. A., Impérato, A., Pedrazzini, T., Roques, B. P., et al. (1999) · Science · doi:10.1126/science.283.5400.401 · Cited by 3,612 · see citing works
Determination and characterization of a cannabinoid receptor in rat brain
Devane, W. A., Dysarz, F. A., Johnson, M. R., Melvin, L. S., & Howlett, A. C. (1988) · Molecular Pharmacology · doi:10.1016/s0026-895x(25)09876-1 · Cited by 2,443 · see citing works
The molecular logic of endocannabinoid signalling
Piomelli, D. (2003) · Nature Reviews Neuroscience · doi:10.1038/nrn1247 · Cited by 1,957 · see citing works
Modulation of anxiety through blockade of anandamide hydrolysis
Kathuria, S., Gaetani, S., Fegley, D., Valiño, F., Duranti, A., Tontini, A., Mor, M., Tarzia, G., Rana, G. L., Calignano, A., et al. (2003) · Nature Medicine · doi:10.1038/nm803 · Cited by 1,293 · see citing works
Increased mortality, hypoactivity, and hypoalgesia in cannabinoid CB1 receptor knockout mice
Zimmer, A., Zimmer, A. M., Hohmann, A. G., Herkenham, M. A., & Bonner, T. I. (1999) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.96.10.5780 · Cited by 1,065 · see citing works
The effects of cannabinoids on the brain
Ameri, A. (1999) · Progress in Neurobiology · doi:10.1016/s0301-0082(98)00087-2 · Cited by 805 · see citing works
Cannabinoid receptors and pain
Pertwee, R. G. (2001) · Progress in Neurobiology · doi:10.1016/s0301-0082(00)00031-9 · Cited by 741 · see citing works
Involvement of CB1 cannabinoid receptors in emotional behaviour
Martín, M., Ledent, C. A., Parmentier, M., Maldonado, R. J., & Valverde, O. (2002) · Psychopharmacology · doi:10.1007/s00213-001-0946-5 · Cited by 507 · see citing works
Takeda, H., Tsuji, M., & Matsumiya, T. (1998) · European Journal of Pharmacology · doi:10.1016/s0014-2999(98)00223-4 · Cited by 461 · see citing works
Defensive burying in rodents: ethology, neurobiology and psychopharmacology
de Boer, S. F., & Koolhaas, J. M. (2003) · European Journal of Pharmacology · doi:10.1016/s0014-2999(03)01278-0 · Cited by 391 · see citing works
Burying as a defensive response in rats.
Pinel, J. P. J., & Treit, D. (1978) · Journal of Comparative and Physiological Psychology · doi:10.1037/h0077494 · Cited by 365 · see citing works
The effects of genetic and pharmacological blockade of the CB1 cannabinoid receptor on anxiety
Haller, J., Bakos, N., Szirmay, M., Ledent, C., & Freund, T. F. (2002) · European Journal of Neuroscience · doi:10.1046/j.1460-9568.2002.02192.x · Cited by 354 · see citing works
Burying as a defensive response in rats
Treit, D. (2010) · cIRcle (University of British Columbia) · doi:10.14288/1.0100236 · Cited by 349 · see citing works
Behavioural and biochemical evidence for interactions between Δ9‐tetrahydrocannabinol and nicotine
Valjent, E., Mitchell, J., Besson, M., Caboche, J., & Maldonado, R. J. (2002) · British Journal of Pharmacology · doi:10.1038/sj.bjp.0704479 · Cited by 321 · see citing works
Navarro, M., Hernández, E., Muñoz, R. M., del Arco, I., Villanúa, M. Á., Carrera, M. R. A., & de Fonseca, F. R. (1997) · Neuroreport · doi:10.1097/00001756-199701200-00023 · Cited by 306 · see citing works
Therapeutic aspects of cannabis and cannabinoids
Robson, P. (2001) · The British Journal of Psychiatry · doi:10.1192/bjp.178.2.107 · Cited by 265 · see citing works
A community survey of adverse effects of cannabis use
Thomas, H. (1996) · Drug and Alcohol Dependence · doi:10.1016/s0376-8716(96)01277-x · Cited by 217 · see citing works
The Functional Neuroanatomy of Brain Cannabinoid Receptors
Breivogel, C. S., & Childers, S. R. (1998) · Neurobiology of Disease · doi:10.1006/nbdi.1998.0229 · Cited by 195 · see citing works
Enhancement of memory in cannabinoid CB1 receptor knock-out mice
Reibaud, M., Obinu, M. C., Ledent, C. A., Parmentier, M., Böhme, G. A., & Impérato, A. (1999) · European Journal of Pharmacology · doi:10.1016/s0014-2999(99)00496-3 · Cited by 189 · see citing works
de Fonseca, F. R., Rubio, P., Menzaghi, F., Merlo‐Pich, E., Rivier, J., Koob, G. F., & Navarro, M. A. (1996) · Journal of Pharmacology and Experimental Therapeutics · doi:10.1016/s0022-3565(25)12276-3 · Cited by 175 · see citing works
SR 141716A enhances spatial memory as assessed in a radial-arm maze task in rats
Lichtman, A. H. (2000) · European Journal of Pharmacology · doi:10.1016/s0014-2999(00)00615-4 · Cited by 171 · see citing works
de Boer, S. F., Slangen, J. L., & van der Gugten, J. (1990) · Physiology & Behavior · doi:10.1016/0031-9384(90)90357-a · Cited by 158 · see citing works
Tzavara, E. T., Wade, M. R., & Nomikos, G. G. (2003) · Journal of Neuroscience · doi:10.1523/jneurosci.23-28-09374.2003 · Cited by 151 · see citing works
Self-citationGessa, G. L., Casu, M. A., Carta, G., & Mascia, M. S. (1998) · European Journal of Pharmacology · doi:10.1016/s0014-2999(98)00486-5 · Cited by 142 · see citing works
Treit, D., Pesold, C., & Rotzinger, S. (1993) · Behavioral Neuroscience · doi:10.1037//0735-7044.107.5.770 · Cited by 137 · see citing works
Dissociations among the anxiolytic effects of septal, hippocampal, and amygdaloid lesions.
Treit, D., & Menard, J. L. (1997) · Behavioral Neuroscience · doi:10.1037//0735-7044.111.3.653 · Cited by 128 · see citing works
Serotonin and acetylcholine release response in the rat hippocampus during a spatial memory task
Stancampiano, R., Cocco, S., Cugusi, C., Sarais, L., & Fadda, F. (1999) · Neuroscience · doi:10.1016/s0306-4522(98)00397-2 · Cited by 125 · see citing works
Hippocampal acetylcholine release correlates with spatial learning performance in freely moving rats
Fadda, F., Cocco, S., & Stancampiano, R. (2000) · Neuroreport · doi:10.1097/00001756-200007140-00040 · Cited by 122 · see citing works
Degroot, A., & Treit, D. (2002) · Brain Research · doi:10.1016/s0006-8993(02)02965-7 · Cited by 121 · see citing works
Self-citationBuspirone impairment of performance of passive avoidance and spatial learning tasks in the rat
Rowan, M. J., Cullen, W. K., & Moulton, B. (1990) · Psychopharmacology · doi:10.1007/bf02244613 · Cited by 115 · see citing works
Sluyter, F., Korte, S. M., Bohus, B., & van Oortmerssen, G. A. (1996) · Pharmacology Biochemistry and Behavior · doi:10.1016/0091-3057(95)02164-7 · Cited by 115 · see citing works
Valverde, O., Ledent, C. A., Beslot, F., Parmentier, M., & Roques, B. P. (2000) · European Journal of Neuroscience · doi:10.1046/j.1460-9568.2000.00929.x · Cited by 111 · see citing works
Silva, G. E. D., & Takahashi, R. N. (2002) · Progress in Neuro-Psychopharmacology and Biological Psychiatry · doi:10.1016/s0278-5846(01)00275-5 · Cited by 110 · see citing works
Degroot, A., Kashluba, S., & Treit, D. (2001) · Pharmacology Biochemistry and Behavior · doi:10.1016/s0091-3057(01)00541-x · Cited by 109 · see citing works
Self-citationTreit, D., Pesold, C., & Rotzinger, S. (1993) · Behavioral Neuroscience · doi:10.1037/0735-7044.107.5.770 · Cited by 109 · see citing works
Pesold, C., & Treit, D. (1992) · Physiology & Behavior · doi:10.1016/0031-9384(92)90431-z · Cited by 106 · see citing works
Dissociations among the anxiolytic effects of septal, hippocampal, and amygdaloid lesions.
Treit, D., & Menard, J. L. (1997) · Behavioral Neuroscience · doi:10.1037/0735-7044.111.3.653 · Cited by 104 · see citing works
SR141716A, a cannabinoid CB1 receptor antagonist, improves memory in a delayed radial maze task
Wolff, M. C., & Leander, J. D. (2003) · European Journal of Pharmacology · doi:10.1016/j.ejphar.2003.08.025 · Cited by 103 · see citing works
Farr, S. A., Flood, J. F., & Morley, J. E. (2000) · Neurobiology of Learning and Memory · doi:10.1006/nlme.1999.3927 · Cited by 96 · see citing works
Kopf, S. R., Buchholzer, M.-L., Hilgert, M., Löffelholz, K., & Klein, J. (2001) · Neuroscience · doi:10.1016/s0306-4522(01)00007-0 · Cited by 89 · see citing works
Rodgers, R. J., Haller, J., Halász, J., & Mikics, É. (2003) · European Journal of Neuroscience · doi:10.1046/j.1460-9568.2003.02548.x · Cited by 88 · see citing works
A comparison of anxiolytic and nonanxiolytic agents in the shock-probe/burying test for anxiolytics
Treit, D. (1990) · Pharmacology Biochemistry and Behavior · doi:10.1016/0091-3057(90)90151-7 · Cited by 86 · see citing works
Role of the amygdala, hippocampus and entorhinal cortex in memory consolidation and expression.
Izquierdo, I., & Medina, J. H. (1993) · PubMed · Cited by 76 · see citing works
Carta, G., Nava, F. A., & GESSA, G. L. (1998) · Brain Research · doi:10.1016/s0006-8993(98)00738-0 · Cited by 67 · see citing works
Septal gabaergic and hippocampal cholinergic systems interact in the modulation of anxiety
Degroot, A., & Treit, D. (2003) · Neuroscience · doi:10.1016/s0306-4522(02)00651-6 · Cited by 60 · see citing works
Self-citationThe contrasting effects of diazepam and yohimbine on conditioned defensive burying in rats
Tsuda, A., Ida, Y., & Tanaka, M. (1988) · Psychobiology · doi:10.3758/bf03327309 · Cited by 53 · see citing works
Kathmann, M., Weber, B., & Schlicker, E. (2001) · Naunyn-Schmiedeberg s Archives of Pharmacology · doi:10.1007/s002100000304 · Cited by 50 · see citing works
Frye, C. A., & Seliga, A. (2003) · Psychoneuroendocrinology · doi:10.1016/s0306-4530(02)00049-5 · Cited by 38 · see citing works
Tohyama, K., Nabeshima, T., Ichihara, K., & Kameyama, T. (1991) · Psychopharmacology · doi:10.1007/bf02316859 · Cited by 22 · see citing works
Irving, A. J., Rae, M. G., & Coutts, A. A. (2002) · The Scientific World JOURNAL · doi:10.1100/tsw.2002.139 · Cited by 21 · see citing works
Sikirić, P., Jelovac, N., Jelovac-Gjeldum, A., et al. (2001) · PubMed · Cited by 19 · see citing works
Cole, B. J., & Jones, G. H. (1995) · Psychopharmacology · doi:10.1007/bf02245247 · Cited by 18 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
The ascent of mouse: advances in modelling human depression and anxiety
Cryan, J. F., & Holmes, A. (2005) · Nature Reviews Drug Discovery · doi:10.1038/nrd1825 · Cited by 1,198 · see citing works
Resolving the neural circuits of anxiety
Calhoon, G. G., & Tye, K. M. (2015) · Nature Neuroscience · doi:10.1038/nn.4101 · Cited by 766 · see citing works
Patel, S., Roelke, C. T., Rademacher, D. J., & Hillard, C. J. (2005) · European Journal of Neuroscience · doi:10.1111/j.1460-9568.2005.03916.x · Cited by 297 · see citing works
Effects of endocannabinoid system modulation on cognitive and emotional behavior
Zanettini, C. (2011) · Frontiers in Behavioral Neuroscience · doi:10.3389/fnbeh.2011.00057 · Cited by 214 · see citing works
Chapter 4.5 The endocannabinoid system and anxiety responses
Bortolato, M., & Piomelli, D. (2008) · Handbook of Behavioral Neuroscience · doi:10.1016/s1569-7339(07)00014-8 · Cited by 7 · see citing works
- Authors
- Degroot, A., & Nomikos, G. G.
- Affiliations
- Eli Lilly (United States) (US)
- ORCID
- Nomikos, George G.
- Venue
- European Journal of Neuroscience
- Publisher
- Wiley
- Published
- 2004-08
- Volume
- 20
- Issue
- 4
- Pages
- 1059-1064
- ISSN
- 0953-816X (ISSN-L)
- 1460-9568
- OpenAlex
- W1966096012
- Cited by
- 58
- References
- 53
- Citations by year
- 2026: 1 · 2025: 4 · 2023: 3 · 2021: 1 · 2020: 3 · 2018: 1 · 2017: 1 · 2016: 1 · 2015: 8 · 2013: 2 · 2012: 4
- FWCI
- 3.98
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- European Journal of Neuroscience (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Pharmacology › Cannabis and Cannabinoid Research
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Keywords
- CB1 receptor, cannabinoid receptors, anxiety, active avoidance, passive avoidance, freezing behavior, CB1 knockout mice, SR141716A, chlordiazepoxide, cognitive performance
- MeSH terms
- Rimonabant, Animals, Anxiety, Carbolines, Chlordiazepoxide, Electroshock, Male, Mice, Inbred C57BL, Piperidines, Pyrazoles, Gene Deletion, Mice, Knockout, Receptor, Cannabinoid, CB1, Mice
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