Upregulation of CB1 receptor binding in the ventromedial prefrontal cortex promotes proactive stress-coping strategies following chronic stress exposure
Open accessAbstract
Accumulating evidence has revealed that dysregulation of the endocannabinoid system could contribute to the development of major depression. Studies carried out post-mortem in depressed suicide victims have revealed increased CB(1) receptor binding site density in the prefrontal cortex (PFC). Accordingly, exposure of rodents to chronic unpredictable stress (CUS) results in phenotypic changes that mirror those of human depression, including increased CB(1) receptor binding site density in the PFC. Our goal in these studies was to examine the effects of CUS on the density of CB(1) receptor binding sites in the rodent medial PFC and to explore the role of this alteration in the behavioral changes invoked by CUS. Rodents exposed to CUS exhibited increased CB(1) receptor maximal binding site density (B(max)) within the ventromedial PFC, but not the dorsomedial PFC. To determine whether this change in the ventromedial PFC is an adaptive response, or alternatively, a consequence of chronic stress that contributes to the adoption of passive coping, we examined whether local CB(1) receptor blockade within the ventromedial PFC following CUS would significantly alter behaviors in the forced swim test (FST). CUS exposure significantly increased passive coping in the FST, and this was further augmented by discrete ventromedial PFC microinfusions of the CB(1) receptor antagonist AM251 prior to swim stress. Moreover, local CB(1) receptor blockade reduced active coping responses in CUS-exposed rats. These findings suggest that the increase in CB(1) receptor B(max) observed in the ventromedial PFC of rodents exposed to CUS maintains proactive coping strategies following chronic stress exposure.
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
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.
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
The rat brain in stereotaxic coordinates
Palkovits, M. (1983) · Neuropeptides · doi:10.1016/0143-4179(83)90049-5 · Cited by 28,959 · see citing works
The Rat Brain in Stereotaxic Coordinates
Paxinos, G., & Watson, C. (1983) · Elsevier eBooks · doi:10.1016/c2009-0-63235-9 · Cited by 28,585 · see citing works
Drevets, W. C., Price, J. L., & Furey, M. L. (2008) · Brain Structure and Function · doi:10.1007/s00429-008-0189-x · Cited by 2,209 · cited 2× · see citing works
“Moreover, a variety of clinical interventions including pharmacological antidepressants, electroconvulsive shock treatment, and deep brain stimulation have all been associated with changes in activity in the SCG coinciding with symptom improvement [28].”
BackgroundWillner, P. (2005) · Neuropsychobiology · doi:10.1159/000087097 · Cited by 1,605 · see citing works
Role of Endogenous Cannabinoids in Synaptic Signaling
Freund, T. F., Katona, I., & Piomelli, D. (2003) · Physiological Reviews · doi:10.1152/physrev.00004.2003 · Cited by 1,567 · see citing works
Cryan, J. F., Valentino, R. J., & Lucki, I. (2005) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2005.03.008 · Cited by 1,115 · see citing works
Architectonic subdivision of the human orbital and medial prefrontal cortex
Öngür, D., Ferry, A. T., & Price, J. L. (2003) · Journal of Comparative Neurology · doi:10.1002/cne.10609 · Cited by 944 · see citing works
Antidepressant effect of optogenetic stimulation of the medial prefrontal cortex
Covington, H. E., Lobo, M. K., Maze, I., Vialou, V., Hyman, J. M., Zaman, S., LaPlant, Q., Mouzon, E., Ghose, S., Tamminga, C. A., et al. (2010) · The Journal of Neuroscience · doi:10.1523/jneurosci.1731-10.2010 · Cited by 621 · see citing works
The subcallosal cingulate gyrus in the context of major depression
Hamani, C., Mayberg, H., Stone, S., Laxton, A., Haber, S., & Lozano, A. M. (2011) · Biological Psychiatry · doi:10.1016/j.biopsych.2010.09.034 · Cited by 508 · see citing works
Endocannabinoids Potentiate Synaptic Transmission through Stimulation of Astrocytes
Navarrete, M., & Araque, A. (2010) · Neuron · doi:10.1016/j.neuron.2010.08.043 · Cited by 485 · see citing works
Neurobiology of chronic mild stress: parallels to major depression
Hill, M. N., Hellemans, K. G. C., Verma, P., Gorzalka, B. B., & Weinberg, J. (2012) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2012.07.001 · Cited by 420 · see citing works
Self-citationHill, M. N., Patel, S., Carrier, E. J., Rademacher, D. J., Ormerod, B. K., Hillard, C. J., & Gorzalka, B. B. (2005) · Neuropsychopharmacology · doi:10.1038/sj.npp.1300601 · Cited by 363 · see citing works
Self-citationHill, M. N., McLaughlin, R. J., Pan, B., Fitzgerald, M. L., Roberts, C. J., Lee, T. T. Y., Karatsoreos, I. N., Mackie, K., Viau, V., Pickel, V. M., et al. (2011) · Journal of Neuroscience · doi:10.1523/jneurosci.0496-11.2011 · Cited by 357 · see citing works
Self-citationBortolato, M., Mangieri, R. A., Fu, J., Kim, J. H., Arguello, O., Duranti, A., Tontini, A., Mor, M., Tarzia, G., & Piomelli, D. (2007) · Biological Psychiatry · doi:10.1016/j.biopsych.2006.12.001 · Cited by 347 · see citing works
Bambico, F. R., Katz, N., Debonnel, G., & Gobbi, G. (2007) · The Journal of Neuroscience · doi:10.1523/jneurosci.1636-07.2007 · Cited by 325 · see citing works
Antidepressant-Like Effects of Medial Prefrontal Cortex Deep Brain Stimulation in Rats
Hamani, C., Diwan, M., Macedo, C. E., Brandão, M. L., Shumake, J., Gonzalez-Lima, F., Raymond, R., Lozano, A. M., Fletcher, P. J., & Nobrega, J. N. (2010) · Biological Psychiatry · doi:10.1016/j.biopsych.2009.08.025 · Cited by 324 · see citing works
Campolongo, P., Roozendaal, B., Trezza, V., Hauer, D., Schelling, G., McGaugh, J. L., & Cuomo, V. (2009) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0900835106 · Cited by 294 · see citing works
Role in Anxiety Behavior of the Endocannabinoid System in the Prefrontal Cortex
Rubino, T., Realini, N., Castiglioni, C., Guidali, C., Viganò, D., Marras, E., Petrosino, S., Perletti, G., Maccarrone, M., Marzo, V. D., et al. (2007) · Cerebral Cortex · doi:10.1093/cercor/bhm161 · Cited by 283 · see citing works
Hill, M. N., Carrier, E. J., McLaughlin, R. J., Morrish, A. C., Meier, S. E., Hillard, C. J., & Gorzalka, B. B. (2008) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.2008.05567.x · Cited by 246 · see citing works
Self-citationReich, C. G., Taylor, M. E., & McCarthy, M. M. (2009) · Behavioural Brain Research · doi:10.1016/j.bbr.2009.05.013 · Cited by 244 · see citing works
Rademacher, D. J., Meier, S. E., Shi, L., Vanessa Ho, W.-S., Jarrahian, A., & Hillard, C. J. (2008) · Neuropharmacology · doi:10.1016/j.neuropharm.2007.06.012 · Cited by 233 · see citing works
Self-citationHungund, B. L., Vinod, K. Y., Kassir, S. A., Basavarajappa, B. S., Yalamanchili, R., Cooper, T. B., Mann, J. J., & Arango, V. (2004) · Molecular Psychiatry · doi:10.1038/sj.mp.4001376 · Cited by 226 · see citing works
Hill, M. N., Kumar, S. A., Filipski, S. B., Iverson, M., Stuhr, K. L., Keith, J. M., Cravatt, B. F., Hillard, C. J., Chattarji, S., & McEwen, B. S. (2013) · Molecular Psychiatry · doi:10.1038/mp.2012.90 · Cited by 222 · see citing works
Self-citationHill, M. N., & Gorzalka, B. B. (2005) · Behavioural Pharmacology · doi:10.1097/00008877-200509000-00006 · Cited by 193 · see citing works
Self-citationVinod, K. Y., Arango, V., Xie, S., Kassir, S. A., Mann, J. J., Cooper, T. B., & Hungund, B. L. (2005) · Biological Psychiatry · doi:10.1016/j.biopsych.2004.11.033 · Cited by 127 · see citing works
Gorzalka, B. B., & Hill, M. N. (2010) · Progress in Neuro-Psychopharmacology and Biological Psychiatry · doi:10.1016/j.pnpbp.2010.11.021 · Cited by 118 · see citing works
Self-citationRegulatory Role of Cannabinoid Receptor 1 in Stress-Induced Excitotoxicity and Neuroinflammation
Zoppi, S., Perez‐Nievas, B. G., Madrigal, J. L. M., Manzanares, J., Leza, J. C., & García‐Bueno, B. (2010) · Neuropsychopharmacology · doi:10.1038/npp.2010.214 · Cited by 116 · see citing works
McLaughlin, R. J., Hill, M. N., Bambico, F. R., Stuhr, K. L., Gobbi, G., Hillard, C. J., & Gorzalka, B. B. (2012) · European Neuropsychopharmacology · doi:10.1016/j.euroneuro.2012.01.004 · Cited by 113 · see citing works
Self-citationChoi, K. H., Le, T., McGuire, J. L., Xing, G., Zhang, L., Li, H., Parker, C. C., Johnson, L. R., & Ursano, R. J. (2012) · Journal of Psychiatric Research · doi:10.1016/j.jpsychires.2012.03.021 · Cited by 83 · see citing works
Cannabinoids and emotionality: a neuroanatomical perspective
McLaughlin, R. J., & Gobbi, G. (2011) · Neuroscience · doi:10.1016/j.neuroscience.2011.07.052 · Cited by 82 · see citing works
Self-citationHillard, C. J., Edgemond, W. S., & Campbell, W. B. (1995) · Journal of Neurochemistry · doi:10.1046/j.1471-4159.1995.64020677.x · Cited by 80 · see citing works
Self-citationMcLaughlin, R. J., Hill, M. N., Morrish, A. C., & Gorzalka, B. B. (2007) · Behavioural Pharmacology · doi:10.1097/fbp.0b013e3282ee7b44 · Cited by 77 · see citing works
Self-citationRodríguez‐Gaztelumendi, A., Rojo, M. L., Pazos, Á., & Díaz, Á. (2009) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.2009.05898.x · Cited by 68 · see citing works
Modulation of pyramidal cell output in the medial prefrontal cortex by mGluR5 interacting with CB1
Kiritoshi, T., Sun, H., Ren, W., Stauffer, S. R., Lindsley, C. W., Conn, P. J., & Neugebauer, V. (2012) · Neuropharmacology · doi:10.1016/j.neuropharm.2012.03.024 · Cited by 50 · see citing works
Expression and Function of the Endocannabinoid System in Glial Cells
Massi, P., Valenti, M., Bolognini, D., et al. (2008) · Current Pharmaceutical Design · doi:10.2174/138161208785740135 · Cited by 28 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Prefrontal cortex and depression
Pizzagalli, D. A., & Roberts, A. C. (2022) · Neuropsychopharmacology · doi:10.1038/s41386-021-01101-7 · Cited by 644 · see citing works
Endocannabinoid system, stress and HPA axis
Micale, V., & Drago, F. (2018) · European Journal of Pharmacology · doi:10.1016/j.ejphar.2018.07.039 · Cited by 189 · see citing works
Ceccarini, J., Hompes, T., Verhaeghen, A., Casteels, C., Peuskens, H., Bormans, G., Claes, S., & Van Laere, K. (2014) · The Journal of Neuroscience · doi:10.1523/jneurosci.0849-13.2014 · Cited by 111 · see citing works
- Authors
- McLaughlin, R. J., Hill, M. N., Dang, S. S., Wainwright, S. R., Galea, L. A. M., Hillard, C. J., & Gorzalka, B. B.
- Affiliations
- University of British Columbia (CA)
- University of Calgary (CA)
- Medical College of Wisconsin (US)
- Corresponding author
- McLaughlin, R.J.
- Venue
- Behavioural Brain Research
- Publisher
- Elsevier BV
- Published
- 2013-01
- Volume
- 237
- Pages
- 333-337
- ISSN
- 0166-4328 (ISSN-L)
- PMC
- PMC3501995
- OpenAlex
- W2039316705
- Cited by
- 65
- References
- 35
- Citations by year
- 2026: 2 · 2025: 3 · 2024: 4 · 2023: 3 · 2022: 4 · 2021: 7 · 2020: 8 · 2019: 1 · 2018: 7 · 2017: 5 · 2016: 3 · 2015: 8 · 2014: 7 · 2013: 2 · 2012: 1
- FWCI
- 4.23
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Behavioural Brain Research (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- Canadian Institutes of Health Research (CIHR)
- National Institutes of Health (DA026996)
- Natural Sciences and Engineering Research Council of Canada
- Topics
- Health Sciences › Medicine › Pharmacology › Cannabis and Cannabinoid Research
- Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
- Health Sciences › Medicine › Pharmacology › Treatment of Major Depression
- Keywords
- CB1 receptor, endocannabinoid system, ventromedial prefrontal cortex, chronic unpredictable mild stress, proactive coping, passive coping, forced swim test, AM251, major depressive disorder, receptor binding density
- MeSH terms
- Adaptation, Psychological, Analgesics, Animals, Cues, Cyclohexanols, Disease Models, Animal, Male, Protein Binding, Stress, Psychological, Swimming, Tritium, Up-Regulation, Rats, Sprague-Dawley, Prefrontal Cortex, Receptor, Cannabinoid, CB1, Rats
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
