{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,1]],"date-time":"2026-11-01T02:40:40Z","timestamp":1793500840651,"version":"4.5.0"},"reference-count":60,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2024,4,3]],"date-time":"2024-04-03T00:00:00Z","timestamp":1712102400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"the General Secretariat for Research and Technology (GSRT) and the Hellenic Foundation for Research and Innovation (HFRI)","award":["95144"],"award-info":[{"award-number":["95144"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Brain Sciences"],"abstract":"<jats:p>Stress-related mental disorders have become increasingly prevalent, thus endangering mental health worldwide. Exploring stress-associated brain alterations is vital for understanding the possible neurobiological mechanisms underlying these changes. Based on existing evidence, the brain endogenous cannabinoid system (ECS) plays a significant role in the stress response, and disruptions in its function are associated with the neurobiology of various stress-related disorders. This study primarily focuses on investigating the impact of chronic unpredictable stress (CUS) on the expression of hippocampal cannabinoid type 1 (CB1) receptors, part of the ECS, in adult male and female Wistar rats. Additionally, it explores whether environmental enrichment (EE) initiated during adolescence could mitigate the CUS-associated alterations in CB1 expression. Wistar rats, shortly after weaning, were placed in either standard housing (SH) or EE conditions for a duration of 10 weeks. On postnatal day 66, specific subgroups of SH or EE animals underwent a 4-week CUS protocol. Western blot (WB) analysis was conducted in the whole hippocampus of the left brain hemisphere to assess total CB1 protein expression, while immunohistochemistry (IHC) was performed on the right hemisphere to estimate the expression of CB1 receptors in certain hippocampal areas (i.e., CA1, CA3 and dentate gyrus-DG). The WB analysis revealed no statistically significant differences in total CB1 protein levels among the groups; however, reduced CB1 expression was found in specific hippocampal sub-regions using IHC. Specifically, CUS significantly decreased CB1 receptor expression in the CA1 and DG of both sexes, whereas in CA3 the CUS-associated decrease was limited to SH males. Interestingly, EE housing proved protective against these reductions. These findings suggest a region and sex-specific endocannabinoid response to chronic stress, emphasizing the role of positive early experiences in the protection of the adolescent brain against adverse conditions later in life.<\/jats:p>","DOI":"10.3390\/brainsci14040357","type":"journal-article","created":{"date-parts":[[2024,4,3]],"date-time":"2024-04-03T00:58:38Z","timestamp":1712105918000},"page":"357","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Sex-Specific Differences and the Role of Environmental Enrichment in the Expression of Hippocampal CB1 Receptors following Chronic Unpredictable Stress"],"prefix":"10.3390","volume":"14","author":[{"given":"Evgenia","family":"Dandi","sequence":"first","affiliation":[{"name":"Laboratory of Cognitive Neuroscience, School of Psychology, Aristotle University of Thessaloniki, 54124 Thessaloniki, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7234-2462","authenticated-orcid":false,"given":"Evangelia","family":"Kesidou","sequence":"additional","affiliation":[{"name":"Laboratory of Experimental Neurology and Neuroimmunology, 2nd Department of Neurology, AHEPA University Hospital, Aristotle University of Thessaloniki, 54636 Thessaloniki, Greece"},{"name":"Laboratory of Physiology, School of Medicine, Aristotle University of Thessaloniki, 54124 Thessaloniki, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Constantina","family":"Simeonidou","sequence":"additional","affiliation":[{"name":"Laboratory of Physiology, School of Medicine, Aristotle University of Thessaloniki, 54124 Thessaloniki, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Evangelia","family":"Spandou","sequence":"additional","affiliation":[{"name":"Laboratory of Physiology, School of Medicine, Aristotle University of Thessaloniki, 54124 Thessaloniki, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4278-3301","authenticated-orcid":false,"given":"Nikolaos","family":"Grigoriadis","sequence":"additional","affiliation":[{"name":"Laboratory of Experimental Neurology and Neuroimmunology, 2nd Department of Neurology, AHEPA University Hospital, Aristotle University of Thessaloniki, 54636 Thessaloniki, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5563-4017","authenticated-orcid":false,"given":"Despina A.","family":"Tata","sequence":"additional","affiliation":[{"name":"Laboratory of Cognitive Neuroscience, School of Psychology, Aristotle University of Thessaloniki, 54124 Thessaloniki, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,4,3]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Knezevic, E., Nenic, K., Milanovic, V., and Knezevic, N.N. (2023). The Role of Cortisol in Chronic Stress, Neurodegenerative Diseases, and Psychological Disorders. Cells, 12.","DOI":"10.3390\/cells12232726"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"2209","DOI":"10.1111\/brv.12750","article-title":"Chronic Stress and Alzheimer\u2019s Disease: The Interplay between the Hypothalamic\u2013Pituitary\u2013Adrenal Axis, Genetics and Microglia","volume":"96","author":"Porter","year":"2021","journal-title":"Biol. Rev."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"219","DOI":"10.1007\/s00702-018-1947-4","article-title":"Cortisol Levels, Motor, Cognitive and Behavioral Symptoms in Parkinson\u2019s Disease: A Systematic Review","volume":"126","author":"Soares","year":"2019","journal-title":"J. Neural Transm."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"123351","DOI":"10.3389\/fpsyt.2015.00032","article-title":"Is Dysregulation of the HPA-Axis a Core Pathophysiology Mediating Co-Morbid Depression in Neurodegenerative Diseases?","volume":"6","author":"Du","year":"2015","journal-title":"Front. Psychiatry"},{"key":"ref_5","first-page":"45","article-title":"Plasma Cortisol, Brain Amyloid-\u03b2, and Cognitive Decline in Preclinical Alzheimer\u2019s Disease: A 6-Year Prospective Cohort Study","volume":"2","author":"Pietrzak","year":"2017","journal-title":"Biol. Psychiatry Cogn. Neurosci. Neuroimaging"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"68","DOI":"10.1016\/j.ynstr.2016.08.001","article-title":"Reliability of the Chronic Mild Stress Model of Depression: A User Survey","volume":"6","author":"Willner","year":"2017","journal-title":"Neurobiol. Stress"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"e01508","DOI":"10.1002\/brb3.1508","article-title":"Long-Term Stability and Characteristics of Behavioral, Biochemical, and Molecular Markers of Three Different Rodent Models for Depression","volume":"10","author":"Zhu","year":"2019","journal-title":"Brain Behav."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"230","DOI":"10.1016\/j.ejphar.2018.07.039","article-title":"Endocannabinoid System, Stress and HPA Axis","volume":"834","author":"Micale","year":"2018","journal-title":"Eur. J. Pharmacol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"485","DOI":"10.1042\/EBC20190086","article-title":"The Endocannabinoid System","volume":"64","author":"Kilaru","year":"2020","journal-title":"Essays Biochem."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"516","DOI":"10.1016\/j.biopsych.2015.07.028","article-title":"An Introduction to the Endogenous Cannabinoid System","volume":"79","author":"Lu","year":"2016","journal-title":"Biol. Psychiatry"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"105","DOI":"10.1016\/j.neuropharm.2017.06.015","article-title":"The Cannabinoid System and Pain","volume":"124","author":"Woodhams","year":"2017","journal-title":"Neuropharmacology"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"791","DOI":"10.1016\/j.pnpbp.2009.11.001","article-title":"Involvement of the Endocannabinoid System in the Neurobehavioural Effects of Stress and Glucocorticoids","volume":"34","author":"Hill","year":"2010","journal-title":"Prog. Neuro-Psychopharmacol. Biol. Psychiatry"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"430","DOI":"10.1124\/mol.114.094649","article-title":"CB2cannabinoid Receptors as a Therapeutic Target-What Does the Future Hold?","volume":"86","author":"Dhopeshwarkar","year":"2014","journal-title":"Mol. Pharmacol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"4449","DOI":"10.1007\/s00018-016-2300-4","article-title":"The CB2 Receptor and Its Role as a Regulator of Inflammation","volume":"73","author":"Turcotte","year":"2016","journal-title":"Cell. Mol. Life Sci."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"108736","DOI":"10.1016\/j.neuropharm.2021.108736","article-title":"Mechanisms of Endocannabinoid Control of Synaptic Plasticity","volume":"197","author":"Winters","year":"2021","journal-title":"Neuropharmacology"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"825","DOI":"10.1007\/s13311-015-0387-1","article-title":"Cannabidiol as a Potential Treatment for Anxiety Disorders","volume":"12","author":"Blessing","year":"2015","journal-title":"Neurotherapeutics"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"331","DOI":"10.1016\/j.pbb.2005.01.029","article-title":"Endocannabinoid System and Stress and Anxiety Responses","volume":"81","author":"Viveros","year":"2005","journal-title":"Pharmacol. Biochem. Behav."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1016\/j.ntt.2016.09.004","article-title":"Sexually-Dimorphic Alterations in Cannabinoid Receptor Density Depend upon Prenatal\/Early Postnatal History","volume":"58","author":"Frank","year":"2016","journal-title":"Neurotoxicol. Teratol."},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Mikulska, J., Juszczyk, G., Gawro\u0144ska-Grzywacz, M., and Herbet, M. (2021). HPA Axis in the Pathomechanism of Depression and Schizophrenia: New Therapeutic Strategies Based on Its Participation. Brain Sci., 11.","DOI":"10.3390\/brainsci11101298"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"2554","DOI":"10.1016\/j.neubiorev.2013.08.002","article-title":"Cannabinoids and Glucocorticoids Modulate Emotional Memory after Stress","volume":"37","author":"Akirav","year":"2013","journal-title":"Neurosci. Biobehav. Rev."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"380","DOI":"10.1016\/j.smim.2014.04.001","article-title":"Stress Regulates Endocannabinoid-CB1 Receptor Signaling","volume":"26","author":"Hillard","year":"2014","journal-title":"Semin. Immunol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"163","DOI":"10.1016\/bs.irn.2015.09.003","article-title":"Endocannabinoid Regulation of Neuroendocrine Systems","volume":"125","author":"Tasker","year":"2015","journal-title":"Int. Rev. Neurobiol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1007\/978-3-030-57369-0_9","article-title":"Psychiatric Disorders and Cannabinoid Receptors","volume":"Volume 1264","author":"Joshi","year":"2021","journal-title":"Advances in Experimental Medicine and Biology"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1016\/j.neubiorev.2018.12.002","article-title":"Chronic Unpredictable Mild Stress for Modeling Depression in Rodents: Meta-Analysis of Model Reliability","volume":"99","author":"Antoniuk","year":"2019","journal-title":"Neurosci. Biobehav. Rev."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"861","DOI":"10.1016\/0031-9384(94)90316-6","article-title":"Effects of Chronic Mild Stress on Performance in Behavioural Tests Relevant to Anxiety and Depression","volume":"56","author":"Brain","year":"1994","journal-title":"Physiol. Behav."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"2085","DOI":"10.1016\/j.neubiorev.2012.07.001","article-title":"Neurobiology of Chronic Mild Stress: Parallels to Major Depression","volume":"36","author":"Hill","year":"2012","journal-title":"Neurosci. Biobehav. Rev."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"3003","DOI":"10.1111\/ejn.16089","article-title":"\u03a4he Neuroprotective Role of Environmental Enrichment against Behavioral, Morphological, Neuroendocrine and Molecular Changes Following Chronic Unpredictable Mild Stress: A Systematic Review","volume":"58","author":"Dandi","year":"2023","journal-title":"Eur. J. Neurosci."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"134","DOI":"10.1016\/j.neuroscience.2011.07.052","article-title":"Cannabinoids and Emotionality: A Neuroanatomical Perspective","volume":"204","author":"McLaughlin","year":"2012","journal-title":"Neuroscience"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"80","DOI":"10.1038\/npp.2015.166","article-title":"Neurobiological Interactions Between Stress and the Endocannabinoid System","volume":"41","author":"Morena","year":"2016","journal-title":"Neuropsychopharmacology"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"508","DOI":"10.1038\/sj.npp.1300601","article-title":"Downregulation of Endocannabinoid Signaling in the Hippocampus Following Chronic Unpredictable Stress","volume":"30","author":"Hill","year":"2005","journal-title":"Neuropsychopharmacology"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"66","DOI":"10.1016\/j.ejphar.2009.04.048","article-title":"Chronic Stress Differentially Regulates Cannabinoid CB1 Receptor Binding in Distinct Hippocampal Subfields","volume":"614","author":"Hill","year":"2009","journal-title":"Eur. J. Pharmacol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"68","DOI":"10.1016\/j.pbb.2016.11.005","article-title":"Sex-Dependent Influence of Chronic Mild Stress (CMS) on Voluntary Alcohol Consumption; Study of Neurobiological Consequences","volume":"152","author":"Marco","year":"2017","journal-title":"Pharmacol. Biochem. Behav."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"264","DOI":"10.1016\/j.bbr.2009.05.013","article-title":"Differential Effects of Chronic Unpredictable Stress on Hippocampal CB1 Receptors in Male and Female Rats","volume":"203","author":"Reich","year":"2009","journal-title":"Behav. Brain Res."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"111522","DOI":"10.1016\/j.mce.2021.111522","article-title":"Lipid Endocannabinoids in Energy Metabolism, Stress and Developmental Programming","volume":"542","author":"Almeida","year":"2022","journal-title":"Mol. Cell. Endocrinol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"995","DOI":"10.1016\/S2215-0366(19)30401-8","article-title":"Cannabinoids for the Treatment of Mental Disorders and Symptoms of Mental Disorders: A Systematic Review and Meta-Analysis","volume":"6","author":"Black","year":"2019","journal-title":"Lancet Psychiatry"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1016\/j.psyneuen.2017.10.015","article-title":"Pharmacological Augmentation of Endocannabinoid Signaling Reduces the Neuroendocrine Response to Stress","volume":"87","author":"Surkin","year":"2018","journal-title":"Psychoneuroendocrinology"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"114062","DOI":"10.1016\/j.bbr.2022.114062","article-title":"Down-Regulation of NR2B Receptors Contributes to the Analgesic and Antianxiety Effects of Enriched Environment Mediated by Endocannabinoid System in the Inflammatory Pain Mice","volume":"435","author":"Jiang","year":"2022","journal-title":"Behav. Brain Res."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"104707","DOI":"10.1016\/j.beproc.2022.104707","article-title":"Investigating the Role of Environmental Enrichment Initiated in Adolescence against the Detrimental Effects of Chronic Unpredictable Stress in Adulthood: Sex-Specific Differences in Behavioral and Neuroendocrinological Findings","volume":"200","author":"Dandi","year":"2022","journal-title":"Behav. Process."},{"key":"ref_39","doi-asserted-by":"crossref","unstructured":"Dandi, \u0395., Theotokis, P., Petri, M.C., Sideropoulou, V., Spandou, E., and Tata, D.A. (2023). Environmental Enrichment Initiated in Adolescence Restores the Reduced Expression of Synaptophysin and GFAP in the Hippocampus of Chronically Stressed Rats in a Sex-Specific Manner. Dev. Psychobiol., 65.","DOI":"10.1002\/dev.22422"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1016\/j.ijdevneu.2018.03.003","article-title":"Beneficial Effects of Environmental Enrichment on Behavior, Stress Reactivity and Synaptophysin\/BDNF Expression in Hippocampus Following Early Life Stress","volume":"67","author":"Dandi","year":"2018","journal-title":"Int. J. Dev. Neurosci."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"235","DOI":"10.1038\/s41583-019-0120-x","article-title":"Environmental Enrichment, New Neurons and the Neurobiology of Individuality","volume":"20","author":"Kempermann","year":"2019","journal-title":"Nat. Rev. Neurosci."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"246","DOI":"10.1016\/j.bbr.2011.04.002","article-title":"The Impact of Environmental Enrichment in Laboratory Rats--Behavioural and Neurochemical Aspects","volume":"222","author":"Simpson","year":"2011","journal-title":"Behav. Brain Res."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"553","DOI":"10.1177\/15353702231171915","article-title":"Enriched Environment as a Nonpharmacological Neuroprotective Strategy","volume":"248","author":"Ortuzar","year":"2023","journal-title":"Exp. Biol. Med."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"80","DOI":"10.1016\/j.brainres.2011.03.025","article-title":"Early Exposure to Environmental Enrichment Alters the Expression of Genes of the Endocannabinoid System","volume":"1390","author":"Thiriet","year":"2011","journal-title":"Brain Res."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"212","DOI":"10.1016\/j.jpsychires.2022.11.035","article-title":"Targeting Mediodorsal Thalamic CB1 Receptors to Inhibit Dextromethorphan-Induced Anxiety\/Exploratory-Related Behaviors in Rats: The Post-Weaning Effect of Exercise and Enriched Environment on Adulthood Anxiety","volume":"157","author":"Rezayof","year":"2023","journal-title":"J. Psychiatr. Res."},{"key":"ref_46","unstructured":"Paxinos, G., and Watson, C. (2007). The Rat Brain in Stereotaxic Coordinates, Elevier. [6th ed.]."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"137","DOI":"10.1038\/s41586-019-1657-6","article-title":"Sex and Gender Analysis Improves Science and Engineering","volume":"575","author":"Tannenbaum","year":"2019","journal-title":"Nature"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"1","DOI":"10.20982\/tqmp.08.1.p001","article-title":"Decomposing Interactions Using GLM in Combination with the COMPARE, LMATRIX and MMATRIX Subcommands in SPSS","volume":"8","author":"Howell","year":"2012","journal-title":"Tutor. Quant. Methods Psychol."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"NS20220034","DOI":"10.1042\/NS20220034","article-title":"Endocannabinoid Signaling and Epigenetics Modifications in the Neurobiology of Stress-Related Disorders","volume":"7","author":"Coelho","year":"2023","journal-title":"Neuronal Signal."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"217","DOI":"10.1016\/j.jad.2023.03.066","article-title":"High-Frequency Repetitive Transcranial Magnetic Stimulation Regulates Neural Oscillations of the Hippocampus and Prefrontal Cortex in Mice by Modulating Endocannabinoid Signalling","volume":"331","author":"Peng","year":"2023","journal-title":"J. Affect. Disord."},{"key":"ref_51","doi-asserted-by":"crossref","unstructured":"Stachowicz, K. (2023). Deciphering the Mechanisms of Reciprocal Regulation or Interdependence at the Cannabinoid CB1 Receptors and Cyclooxygenase-2 Level: Effects on Mood, Cognitive Implications, and Synaptic Signaling. Neurosci. Biobehav. Rev., 155.","DOI":"10.1016\/j.neubiorev.2023.105439"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"1706","DOI":"10.1016\/S0140-6736(07)61721-8","article-title":"Efficacy and Safety of the Weight-Loss Drug Rimonabant: A Meta-Analysis of Randomised Trials","volume":"370","author":"Christensen","year":"2007","journal-title":"Lancet"},{"key":"ref_53","doi-asserted-by":"crossref","unstructured":"Romero-Torres, B.M., Alvarado-Ram\u00edrez, Y.A., Duran-Alonzo, S.R., Ruiz-Contreras, A.E., Herrera-Solis, A., Amancio-Belmont, O., Prosp\u00e9ro-Garc\u00eda, O.E., and M\u00e9ndez-D\u00edaz, M. (2023). A Potential Role of Hippocampus on Impulsivity and Alcohol Consumption Though CB1R. Pharmacol. Biochem. Behav., 225.","DOI":"10.1016\/j.pbb.2023.173558"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"518","DOI":"10.1016\/j.arcmed.2019.09.005","article-title":"Endocannabinoids as Therapeutic Targets","volume":"50","year":"2019","journal-title":"Arch. Med. Res."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"148378","DOI":"10.1016\/j.brainres.2023.148378","article-title":"Activation of Ventral Hippocampal CB1 Receptors Inhibits Ketamine-Induced Anxiogenic-like Behavior: Alteration of BDNF\/c-Fos Levels in the Mouse Hippocampus","volume":"1810","author":"Alijanpour","year":"2023","journal-title":"Brain Res."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"113133","DOI":"10.1016\/j.physbeh.2020.113133","article-title":"Impact of Enriched Environment during Adolescence on Adult Social Behavior, Hippocampal Synaptic Density and Dopamine D2 Receptor Expression in Rats","volume":"226","author":"Gabriel","year":"2020","journal-title":"Physiol. Behav."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"3373","DOI":"10.1002\/jnr.24974","article-title":"Effects of Short Environmental Enrichment on Early-Life Adversity Induced Cognitive Alternations in Adolescent Rats","volume":"99","author":"Joushi","year":"2021","journal-title":"J. Neurosci. Res."},{"key":"ref_58","first-page":"230","article-title":"Potential Utility of Cannabidiol in Stress-Related Disorders","volume":"8","author":"Lookfong","year":"2023","journal-title":"Cannabis Cannabinoid Res."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"278","DOI":"10.1002\/syn.20844","article-title":"Differential Developmental Trajectories for CB1 Cannabinoid Receptor Expression in Limbic\/Associative and Sensorimotor Cortical Areas","volume":"65","author":"Heng","year":"2011","journal-title":"Synapse"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"1579","DOI":"10.1016\/j.euroneuro.2016.08.010","article-title":"Dorsal Hippocampus Cannabinoid Type 1 Receptors Modulate the Expression of Contextual Fear Conditioning in Rats: Involvement of Local Glutamatergic\/Nitrergic and GABAergic Neurotransmissions","volume":"26","author":"Spiacci","year":"2016","journal-title":"Eur. Neuropsychopharmacol."}],"container-title":["Brain Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2076-3425\/14\/4\/357\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T14:22:44Z","timestamp":1760106164000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2076-3425\/14\/4\/357"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,4,3]]},"references-count":60,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2024,4]]}},"alternative-id":["brainsci14040357"],"URL":"https:\/\/doi.org\/10.3390\/brainsci14040357","relation":{},"ISSN":["2076-3425"],"issn-type":[{"value":"2076-3425","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,4,3]]}}}