{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,28]],"date-time":"2026-08-28T03:27:09Z","timestamp":1787887629801,"version":"build-2784847793"},"reference-count":65,"publisher":"MDPI AG","issue":"20","license":[{"start":{"date-parts":[[2023,10,18]],"date-time":"2023-10-18T00:00:00Z","timestamp":1697587200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"ELTE BDPK Excellence Program","award":["12\/2021"],"award-info":[{"award-number":["12\/2021"]}]},{"name":"ELTE BDPK Excellence Program","award":["12\/2022"],"award-info":[{"award-number":["12\/2022"]}]},{"name":"Ketone Technologies LLC","award":["12\/2021"],"award-info":[{"award-number":["12\/2021"]}]},{"name":"Ketone Technologies LLC","award":["12\/2022"],"award-info":[{"award-number":["12\/2022"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Nutrients"],"abstract":"<jats:p>While one-third of the population can be affected by anxiety disorders during their lifetime, our knowledge of the pathophysiology of these disorders is far from complete. Previously, it has been demonstrated in male animals that exogenous ketone supplement-evoked ketosis can decrease anxiety levels in preclinical rodent models, such as Wistar Albino Glaxo\/Rijswijk (WAG\/Rij) rats. Thus, in this study, we investigated whether intragastric gavage of the exogenous ketone supplement KEMCT (mix of 1,3-butanediol-acetoacetate diester\/ketone ester\/KE and medium-chain triglyceride\/MCT oil in 1:1 ratio) for 7 days can alter the anxiety levels of female WAG\/Rij rats using the light\u2013dark box (LDB) test. We demonstrated that a lower dose of KEMCT (3 g\/kg\/day) increased blood R-\u03b2HB (R-\u03b2-hydroxybutyrate) levels and significantly decreased anxiety levels (e.g., increased the time spent in the light compartment) in female WAG\/Rij rats on the seventh day of administration. Although the higher KEMCT dose (5 g\/kg\/day) increased blood R-\u03b2HB levels more effectively, compared with the lower KEMCT dose, anxiety levels did not improve significantly. We conclude that ketone supplementation might be an effective strategy to induce anxiolytic effects not only in male but also in female WAG\/Rij rats. However, these results suggest that the optimal level may be moderately, not highly, elevated blood R-\u03b2HB levels when the goal is to alleviate symptoms of anxiety. More studies are needed to understand the exact mechanism of action of ketone supplementation on anxiety levels and to investigate their use in other animal models and humans for the treatment of anxiety disorders and other mental health conditions.<\/jats:p>","DOI":"10.3390\/nu15204412","type":"journal-article","created":{"date-parts":[[2023,10,18]],"date-time":"2023-10-18T09:56:57Z","timestamp":1697623017000},"page":"4412","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Dose-Dependent Beneficial Effect of Ketone Supplement-Evoked Ketosis on Anxiety Level in Female WAG\/Rij Rats: Sometimes Less Is More"],"prefix":"10.3390","volume":"15","author":[{"given":"Enik\u0151","family":"Rauch","sequence":"first","affiliation":[{"name":"Department of Biology, Savaria University Centre, E\u00f6tv\u00f6s Lor\u00e1nd University (ELTE), K\u00e1rolyi G\u00e1sp\u00e1r t\u00e9r 4, 9700 Szombathely, Hungary"},{"name":"Institute of Biology, University of P\u00e9cs, Ifj\u00fas\u00e1g Str. 6, 7624 P\u00e9cs, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8677-823X","authenticated-orcid":false,"given":"Csilla","family":"Ari","sequence":"additional","affiliation":[{"name":"Behavioral Neuroscience Research Laboratory, Department of Psychology, University of South Florida, Tampa, FL 33620, USA"},{"name":"Ketone Technologies LLC, Tampa, FL 33612, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8571-5686","authenticated-orcid":false,"given":"Zsolt","family":"Kov\u00e1cs","sequence":"additional","affiliation":[{"name":"Department of Biology, Savaria University Centre, E\u00f6tv\u00f6s Lor\u00e1nd University (ELTE), K\u00e1rolyi G\u00e1sp\u00e1r t\u00e9r 4, 9700 Szombathely, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,10,18]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"327","DOI":"10.31887\/DCNS.2015.17.3\/bbandelow","article-title":"Epidemiology of anxiety disorders in the 21st century","volume":"17","author":"Bandelow","year":"2015","journal-title":"Dialogues Clin. Neurosci."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"318","DOI":"10.1016\/j.tins.2023.01.007","article-title":"Genetic insights into the neurobiology of anxiety","volume":"46","author":"Koskinen","year":"2023","journal-title":"Trends Neurosci."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1142682","DOI":"10.3389\/fpsyt.2023.1142682","article-title":"Exploring the role of ketone bodies in the diagnosis and treatment of psychiatric disorders","volume":"14","author":"Omori","year":"2023","journal-title":"Front. Psychiatry"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"346","DOI":"10.1016\/j.conb.2013.01.013","article-title":"Towards new approaches to disorders of fear and anxiety","volume":"23","author":"Dias","year":"2013","journal-title":"Curr. Opin. Neurobiol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"2127","DOI":"10.1111\/j.1476-5381.1995.tb16421.x","article-title":"Anxiolytic activity of adenosine receptor activation in mice","volume":"1116","author":"Jain","year":"1995","journal-title":"Br. J. Pharmacol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"393","DOI":"10.1016\/j.pbb.2008.12.022","article-title":"Anxiolytic-like profile of mirtazapine in rat conditioned fear stress model: Functional significance of 5-hydroxytryptamine 1A receptor and alpha1-adrenergic receptor","volume":"92","author":"Kakui","year":"2009","journal-title":"Pharmacol. Biochem. Behav."},{"key":"ref_7","first-page":"241","article-title":"Using the conditioned fear stress (CFS) animal model to understand the neurobiological mechanisms and pharmacological treatment of anxiety","volume":"24","author":"Li","year":"2012","journal-title":"Shanghai Arch. Psychiatry"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"93","DOI":"10.31887\/DCNS.2017.19.2\/bbandelow","article-title":"Treatment of anxiety disorders","volume":"19","author":"Bandelow","year":"2017","journal-title":"Dialogues Clin. Neurosci."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"137","DOI":"10.3389\/fnmol.2016.00137","article-title":"Exogenous Ketone Supplements Reduce Anxiety-Related Behavior in Sprague-Dawley and Wistar Albino Glaxo\/Rijswijk Rats","volume":"9","author":"Ari","year":"2016","journal-title":"Front. Mol. Neurosci."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"833","DOI":"10.1007\/s00213-020-05735-1","article-title":"Effects of ketogenic diet and ketone monoester supplement on acute alcohol withdrawal symptoms in male mice","volume":"238","author":"Bornebusch","year":"2021","journal-title":"Psychopharmacology"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"245","DOI":"10.1016\/j.neuropharm.2018.06.017","article-title":"Medium chain triglyceride diet reduces anxiety-like behaviors and enhances social competitiveness in rats","volume":"138","author":"Hollis","year":"2018","journal-title":"Neuropharmacology"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1530","DOI":"10.1016\/j.neurobiolaging.2012.11.023","article-title":"A ketone ester diet exhibits anxiolytic and cognition-sparing properties, and lessens amyloid and tau pathologies in a mouse model of Alzheimer\u2019s disease","volume":"34","author":"Kashiwaya","year":"2013","journal-title":"Neurobiol. Aging"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1186\/s12986-016-0069-y","article-title":"Effects of exogenous ketone supplementation on blood ketone, glucose, triglyceride, and lipoprotein levels in Sprague-Dawley rats","volume":"13","author":"Kesl","year":"2016","journal-title":"Nutr. Metab."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"29","DOI":"10.3389\/fnbeh.2018.00029","article-title":"Anxiolytic Effect of Exogenous Ketone Supplementation Is Abolished by Adenosine A1 Receptor Inhibition in Wistar Albino Glaxo\/Rijswijk Rats","volume":"12","author":"Ari","year":"2018","journal-title":"Front. Behav. Neurosci."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"100","DOI":"10.1152\/ajpregu.00088.2021","article-title":"Exogenous ketone ester delays CNS oxygen toxicity without impairing cognitive and motor performance in male Sprague-Dawley rats","volume":"321","author":"Stavitzski","year":"2021","journal-title":"Am. J. Physiol. Regul. Integr. Comp. Physiol."},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Ari, C., D\u2019Agostino, D.P., Diamond, D.M., Kindy, M., Park, C., and Kov\u00e1cs, Z. (2019). Elevated Plus Maze Test Combined with Video Tracking Software to Investigate the Anxiolytic Effect of Exogenous Ketogenic Supplements. J. Vis. Exp., 143.","DOI":"10.3791\/58396-v"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"363","DOI":"10.3389\/fpsyt.2019.00363","article-title":"Therapeutic Potential of Exogenous Ketone Supplement Induced Ketosis in the Treatment of Psychiatric Disorders: Review of Current Literature","volume":"10","author":"Diamond","year":"2019","journal-title":"Front. Psychiatry"},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Kraeuter, A.K., Phillips, R., and Sarnyai, Z. (2020). Ketogenic therapy in neurodegenerative and psychiatric disorders: From mice to men. Prog. Neuropsychopharmacol. Biol. Psychiatry, 101.","DOI":"10.1016\/j.pnpbp.2020.109913"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"635","DOI":"10.1023\/A:1026179013847","article-title":"Genetic animal models for absence epilepsy: A review of the WAG\/Rij strain of rats","volume":"33","author":"Coenen","year":"2003","journal-title":"Behav. Genet."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"618422","DOI":"10.3389\/fnins.2020.618422","article-title":"Age- and Sex-Dependent Modulation of Exogenous Ketone Supplement-Evoked Effects on Blood Glucose and Ketone Body Levels in Wistar Albino Glaxo Rijswijk Rats","volume":"14","author":"Brunner","year":"2021","journal-title":"Front. Neurosci."},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Sar\u00e9, R.M., Lemons, A., and Smith, C.B. (2021). Behavior Testing in Rodents: Highlighting Potential Confounds Affecting Variability and Reproducibility. Brain Sci., 11.","DOI":"10.3390\/brainsci11040522"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"341","DOI":"10.9758\/cpn.2020.18.3.341","article-title":"A Review of Behavioral Tests to Evaluate Different Types of Anxiety and Anti-anxiety Effects","volume":"18","author":"Himanshu","year":"2020","journal-title":"Clin. Psychopharmacol. Neurosci."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"543","DOI":"10.1016\/j.yebeh.2005.03.005","article-title":"Convulsive and nonconvulsive epilepsy in rats: Effects on behavioral response to novelty stress","volume":"6","author":"Midzyanovskaya","year":"2005","journal-title":"Epilepsy Behav."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"74","DOI":"10.1111\/j.1600-0447.1998.tb05970.x","article-title":"Animal models sensitive to anti-anxiety agents","volume":"393","author":"Martin","year":"1998","journal-title":"Acta Psychiatr. Scand. Suppl."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1477","DOI":"10.1037\/0735-7044.119.6.1477","article-title":"Comparison of anxiety-like behavior in adolescent and adult Sprague-Dawley rats","volume":"119","author":"Slawecki","year":"2005","journal-title":"Behav. Neurosci."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"279","DOI":"10.1016\/j.pbb.2014.04.011","article-title":"Ontogeny and adolescent alcohol exposure in Wistar rats: Open field conflict, light\/dark box and forced swim test","volume":"122","author":"Desikan","year":"2014","journal-title":"Pharmacol. Biochem. Behav."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1016\/j.bbr.2005.07.024","article-title":"Behavioral characteristics of WAG\/Rij rats susceptible and non-susceptible to audiogenic seizures","volume":"166","author":"Sarkisova","year":"2006","journal-title":"Behav. Brain Res."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1016\/0091-3057(95)02130-2","article-title":"Muscarinic antagonists are anxiogenic in rats tested in the black-white box","volume":"54","author":"Smythe","year":"1996","journal-title":"Pharmacol. Biochem. Behav."},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Ari, C., Murdun, C., Koutnik, A.P., Goldhagen, C.R., Rogers, C., Park, C., Bharwani, S., Diamond, D.M., Kindy, M.S., and D\u2019Agostino, D.P. (2019). Exogenous Ketones Lower Blood Glucose Level in Rested and Exercised Rodent Models. Nutrients, 11.","DOI":"10.3390\/nu11102330"},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Kov\u00e1cs, Z., Brunner, B., D\u2019Agostino, D.P., and Ari, C. (2020). Inhibition of adenosine A1 receptors abolished the nutritional ketosis-evoked delay in the onset of isoflurane-induced anesthesia in Wistar Albino Glaxo Rijswijk rats. BMC Anesthesiol., 20.","DOI":"10.1186\/s12871-020-0943-z"},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Kov\u00e1cs, Z., D\u2019Agostino, D.P., and Ari, C. (2023). Ketone supplementation abolished isoflurane anesthesia-induced elevation in blood glucose level and increased recovery time from anesthesia in Wistar Albino Glaxo Rijswijk rats. BMC Anesthesiol., 23.","DOI":"10.1186\/s12871-023-02000-8"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"829","DOI":"10.1152\/ajpregu.00506.2012","article-title":"Therapeutic ketosis with ketone ester delays central nervous system oxygen toxicity seizures in rats","volume":"304","author":"Pilla","year":"2013","journal-title":"Am. J. Physiol. Regul. Integr. Comp. Physiol."},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Ari, C., Murdun, C., Goldhagen, C., Koutnik, A.P., Bharwani, S.R., Diamond, D.M., Kindy, M., D\u2019Agostino, D.P., and Kovacs, Z. (2020). Exogenous Ketone Supplements Improved Motor Performance in Preclinical Rodent Models. Nutrients, 12.","DOI":"10.3390\/nu12082459"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"182","DOI":"10.1186\/1742-2094-9-182","article-title":"Recurrent\/moderate hypoglycemia induces hippocampal dendritic injury, microglial activation, and cognitive impairment in diabetic rats","volume":"9","author":"Won","year":"2012","journal-title":"J. Neuroinflammation"},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Kambe, Y. (2022). Recent behavioral findings of pathophysiological involvement of lactate in the central nervous system. Biochim. Biophys. Acta. Gen. Subj., 1866.","DOI":"10.1016\/j.bbagen.2022.130137"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"1154","DOI":"10.2337\/db22-0902","article-title":"Astrocyte Glycogen Is a Major Source of Hypothalamic Lactate in Rats with Recurrent Hypoglycemia","volume":"72","author":"Su","year":"2023","journal-title":"Diabetes"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"69","DOI":"10.4103\/1673-5374.374142","article-title":"Lactate metabolism in neurodegenerative diseases","volume":"19","author":"Yang","year":"2024","journal-title":"Neural Regen. Res."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"401","DOI":"10.1016\/j.yrtph.2012.04.008","article-title":"Kinetics, safety and tolerability of (R)-3-hydroxybutyl (R)-3-hydroxybutyrate in healthy adult subjects","volume":"63","author":"Clarke","year":"2012","journal-title":"Regul. Toxicol. Pharmacol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"196","DOI":"10.1016\/j.yrtph.2012.04.001","article-title":"Oral 28-day and developmental toxicity studies of (R)-3-hydroxybutyl (R)-3-hydroxybutyrate","volume":"63","author":"Clarke","year":"2012","journal-title":"Regul. Toxicol. Pharmacol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"1719","DOI":"10.1093\/jn\/101.12.1719","article-title":"Metabolic fate of 1,3-butanediol in the rat: Conversion to -hydroxybutyrate","volume":"101","author":"Tate","year":"1971","journal-title":"J. Nutr."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"943","DOI":"10.1194\/jlr.R067629","article-title":"Short- and medium-chain fatty acids in energy metabolism: The cellular perspective","volume":"57","author":"Wojtczak","year":"2016","journal-title":"J. Lipid Res."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1007\/s11064-016-2099-2","article-title":"\u03b2-Hydroxybutyrate in the brain: One molecule, multiple mechanisms","volume":"42","author":"Achanta","year":"2017","journal-title":"Neurochem. Res."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"42","DOI":"10.1016\/j.tem.2013.09.002","article-title":"Ketone bodies as signaling metabolites","volume":"25","author":"Newman","year":"2014","journal-title":"Trends. Endocrinol. Metab."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"1","DOI":"10.14581\/jer.15001","article-title":"Pharmacoresistant epilepsy: A current update on non-conventional pharmacological and non-pharmacological interventions","volume":"5","author":"Sharma","year":"2015","journal-title":"J. Epilepsy Res."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"229","DOI":"10.1016\/j.eplepsyres.2011.07.014","article-title":"Purines and neuronal excitability: Links to the ketogenic diet","volume":"100","author":"Masino","year":"2012","journal-title":"Epilepsy Res."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"104","DOI":"10.1089\/caff.2020.0011","article-title":"Adenosine and Ketogenic Treatments","volume":"10","author":"Ruskin","year":"2020","journal-title":"J. Caffeine Adenosine Res."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1016\/j.brainres.2017.04.010","article-title":"Ischemic preconditioning with a ketogenic diet improves brain ischemic tolerance through increased extracellular adenosine levels and hypoxia-inducible factors","volume":"1667","author":"Yang","year":"2017","journal-title":"Brain Res."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"3886","DOI":"10.1523\/JNEUROSCI.0055-10.2010","article-title":"Metabolic autocrine regulation of neurons involves cooperation among pannexin hemichannels, adenosine receptors, and KATP channels","volume":"30","author":"Kawamura","year":"2010","journal-title":"J. Neurosci."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"299","DOI":"10.1111\/j.1600-0773.1995.tb01031.x","article-title":"Purinergic inhibition of neurotransmitter release in the central nervous system","volume":"77","author":"Ribeiro","year":"1995","journal-title":"Pharmacol. Toxicol."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"2011","DOI":"10.1007\/s11064-017-2253-5","article-title":"Ketone bodies as anti-seizure agents","volume":"42","author":"Simeone","year":"2017","journal-title":"Neurochem. Res."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1016\/j.neuron.2010.09.002","article-title":"Metabolic control of vesicular glutamate transport and release","volume":"68","author":"Juge","year":"2010","journal-title":"Neuron"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"273","DOI":"10.1016\/j.tins.2008.02.009","article-title":"Are purines mediators of the anticonvulsant\/neuroprotective effects of ketogenic diets?","volume":"31","author":"Masino","year":"2008","journal-title":"Trends Neurosci."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"1408","DOI":"10.4088\/JCP.v64n1201","article-title":"Brainstorms: Symptoms and circuits, part 2: Anxiety disorders","volume":"64","author":"Stahl","year":"2003","journal-title":"J. Clin. Psychiatry"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"153","DOI":"10.1007\/s002130050037","article-title":"The anxiogenic-like effect of caffeine in two experimental procedures measuring anxiety in the mouse is not shared by selective A2A adenosine receptor antagonists","volume":"148","author":"Ledent","year":"2000","journal-title":"Psychopharmacology"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"311","DOI":"10.1007\/s002130050572","article-title":"Adenosine A1 receptors modulate anxiety in CD1 mice","volume":"136","author":"Florio","year":"1998","journal-title":"Psychopharmacology"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"443","DOI":"10.1016\/S0006-2952(00)00570-0","article-title":"Comparison of the potency of adenosine as an agonist at human adenosine receptors expressed in Chinese hamster ovary cells","volume":"61","author":"Fredholm","year":"2001","journal-title":"Biochem. Pharmacol."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"2080","DOI":"10.1523\/JNEUROSCI.3574-05.2006","article-title":"Presynaptic control of striatal glutamatergic neurotransmission by adenosine A1-A2A receptor heteromers","volume":"26","author":"Ciruela","year":"2006","journal-title":"J. Neurosci."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"1512","DOI":"10.2174\/138161208784480090","article-title":"Potential therapeutic interest of adenosine A2A receptors in psychiatric disorders","volume":"14","author":"Cunha","year":"2008","journal-title":"Curr. Pharm. Des."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"111","DOI":"10.1007\/s11302-005-0649-1","article-title":"Neuroprotection by adenosine in the brain: From A(1) receptor activation to A (2A) receptor blockade","volume":"1","author":"Cunha","year":"2005","journal-title":"Purinergic Signal."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"760","DOI":"10.1016\/j.biopsych.2005.11.027","article-title":"The benzodiazepine alprazolam dissociates contextual fear from cued fear in humans as assessed by fear-potentiated startle","volume":"60","author":"Grillon","year":"2006","journal-title":"Biol. Psychiatry"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"1118","DOI":"10.1016\/j.biopsych.2008.01.012","article-title":"A meta-analysis of D-cycloserine and the facilitation of fear extinction and exposure therapy","volume":"63","author":"Norberg","year":"2008","journal-title":"Biol. Psychiatry"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"19314","DOI":"10.1523\/JNEUROSCI.3102-13.2013","article-title":"\u03b2-Hydroxybutyrate modulates N-type calcium channels in rat sympathetic neurons by acting as an agonist for the G-protein-coupled receptor FFA3","volume":"33","author":"Won","year":"2013","journal-title":"J. Neurosci."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"295","DOI":"10.31887\/DCNS.2015.17.3\/mbourin","article-title":"Animal models for screening anxiolytic-like drugs: A perspective","volume":"17","author":"Bourin","year":"2015","journal-title":"Dialogues Clin. Neurosci."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"181","DOI":"10.31887\/DCNS.2017.19.2\/wcarlezon","article-title":"Behavioral methods to study anxiety in rodents","volume":"19","author":"Lezak","year":"2017","journal-title":"Dialogues Clin. Neurosci."},{"key":"ref_65","doi-asserted-by":"crossref","unstructured":"Bear, T., Roy, N., Dalziel, J., Butts, C., Coad, J., Young, W., Parkar, S.G., Hedderley, D., Dinnan, H., and Martell, S. (2023). Anxiety-like Behavior in Female Sprague Dawley Rats Associated with Cecal Clostridiales. Microorganisms, 11.","DOI":"10.3390\/microorganisms11071773"}],"container-title":["Nutrients"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6643\/15\/20\/4412\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T21:08:45Z","timestamp":1760130525000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6643\/15\/20\/4412"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,10,18]]},"references-count":65,"journal-issue":{"issue":"20","published-online":{"date-parts":[[2023,10]]}},"alternative-id":["nu15204412"],"URL":"https:\/\/doi.org\/10.3390\/nu15204412","relation":{},"ISSN":["2072-6643"],"issn-type":[{"value":"2072-6643","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,10,18]]}}}