“ADVANCES IN ANXIETY RESEARCH: ASSESSING THE ANXIOLYTIC EFFECTS OF NOVEL COMPOUNDS IN EXPERIMENTAL GAD MODELS”
Main Article Content
Keywords
Generalized Anxiety Disorder, Anxiolytics, Novel Compounds, Rodent Models, GABA-A Receptor, 5-HT1A Receptor, Behavioural Pharmacology
Abstract
Background: Generalized Anxiety Disorder (GAD) is a prevalent and debilitating mental health condition characterized by excessive and persistent worry. Current pharmacological treatments often exhibit delayed onset and undesirable side effects, highlighting the need for more effective and better-tolerated anxiolytic agents.
Objective: This study aimed to evaluate the anxiolytic potential of newly developed compounds using validated experimental models of GAD in preclinical settings.
Methods: A series of novel chemical entities were synthesized and screened for anxiolytic activity using established rodent models, including the Elevated plus Maze (EPM), Open Field Test (OFT), and Light-Dark Box test. Behavioural outcomes were compared against standard anxiolytics such as diazepam. Neurochemical assays and receptor-binding studies were conducted to elucidate the mechanisms of action.
Results: Several novel compounds demonstrated significant anxiolytic-like effects in rodent models without impairing locomotor activity. Preliminary data suggest modulation of GABAergic and serotonergic pathways, with some compounds showing partial agonist activity at the GABA-A receptor and selectivity for 5-HT1A receptors.
Conclusions: The findings support the therapeutic potential of these new compounds as effective anxiolytics with favorable safety profiles. Further pharmacokinetic and clinical investigations are warranted to explore their applicability in human GAD treatment.
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2. Akhondzadeh, S., Kashani, L., Mobaseri, M., et al. (2001). Crocus sativus L. (saffron) in the treatment of mild to moderate depression: A double-blind, randomized and placebo-controlled trial. Phytomedicine, 8(5), 263-267. https://doi.org/10.1078/094471101750257139
3. Atmaca, M. (2010). Neurobiology of anxiety disorders. Psychiatry and Clinical Neurosciences, 64(6), 461-470. https://doi.org/10.1111/j.1440-1819.2010.02109.x
4. Bandelow, B., Michaelis, S., & Wedekind, D. (2017). Treatment of anxiety disorders. Dialogues in Clinical Neuroscience, 19(2), 93-107. https://doi.org/10.31887/DCNS.2017.19.2/bbandelow
5. Basu, A., & Dasgupta, P. S. (2020). Neurobiology of anxiety disorders: Role of neurotransmitters and novel targets. Current Neuropharmacology, 18(10), 1053-1066. https://doi.org/10.2174/1570159X18666200515122639
6. Becker, R., Schmitt, S., & Markou, A. (2017). Translational animal models of anxiety disorders: A focus on generalized anxiety disorder. Current Topics in Behavioural Neurosciences, 30, 75-93. https://doi.org/10.1007/7854_2016_43
7. Biedermann, S., Zeitz, J., Mwinyi, J., et al. (2013). Smoking cessation induces profound changes in the composition of the intestinal microbiota in humans. PLoS One, 8(3), e59260. https://doi.org/10.1371/journal.pone.0059260
8. Bourin, M., & Hascoët, M. (2003). The mouse light/dark box test. European Journal of Pharmacology, 463(1-3), 55-65. https://doi.org/10.1016/S0014-2999(03)01274-3
9. Brühl, A. B., Delsignore, A., Komossa, K., & Weidt, S. (2014). Neuroimaging in social anxiety disorder – A meta-analytic review resulting in a new neurofunctional model. Neuroscience & Biobehavioral Reviews, 47, 260-280. https://doi.org/10.1016/j.neubiorev.2014.08.003
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12. Chen, A. C., & Etkin, A. (2013). Hippocampal network connectivity and activation differentiates post-traumatic stress disorder from generalized anxiety disorder. Neuropsychopharmacology, 38(10), 1889-1898. https://doi.org/10.1038/npp.2013.107
13. Choi, D. Y., & Kim, H. (2017). Phytochemicals in anxiety treatment: A review of evidence from preclinical and clinical studies. Frontiers in Pharmacology, 8, 20. https://doi.org/10.3389/fphar.2017.00020
14. Cryan, J. F., & Sweeney, F. F. (2011). The age of anxiety: Role of the gut microbiota in anxiety and depression. Trends in Neurosciences, 34(8), 427-434. https://doi.org/10.1016/j.tins.2011.05.003
15. Cunha, J. M., & Bortolatto, C. F. (2020). Novel therapeutic targets for anxiety disorders: Insights from rodent models. Progress in Neuro-Psychopharmacology & Biological Psychiatry, 102, 109946. https://doi.org/10.1016/j.pnpbp.2020.109946
16. De Carvalho, R. F., de Almeida, J. R., & Silva, E. R. (2018). Effects of neurosteroids in anxiety: Focus on allopregnanolone analogs. Frontiers in Pharmacology, 9, 675. https://doi.org/10.3389/fphar.2018.00675
17. Di Mauro, M., & Renaldo, L. (2019). Epigenetic modulators as therapeutic targets in anxiety disorders. Neuroscience Letters, 711, 134471. https://doi.org/10.1016/j.neulet.2019.134471
18. Duman, R. S., Aghajanian, G. K., Sanacora, G., & Krystal, J. H. (2016). Synaptic plasticity and depression: New insights from stress and rapid-acting antidepressants. Nature Medicine, 22(3), 238-249. https://doi.org/10.1038/nm.4050
19. Dwyer, J. B., McQuown, S. C., & Leslie, F. M. (2009). The dynamic effects of nicotine on the developing brain. Pharmacology & Therapeutics, 122(2), 125-139. https://doi.org/10.1016/j.pharmthera.2009.02.003
20. Fogaça, M. V., & Duman, R. S. (2019). Cortical gabaergic dysfunction in stress and depression: New insights for novel therapeutic approaches. Neuroscience Letters, 733, 135069. https://doi.org/10.1016/j.neulet.2019.135069
21. Francesconi, W., & Berton, O. (2021). Neuropeptides in anxiety and depression: Therapeutic perspectives. Frontiers in Molecular Neuroscience, 14, 621595. https://doi.org/10.3389/fnmol.2021.621595
22. Gielen, M., & Houwing, D. J. (2018). Microbiota-gut-brain axis in anxiety: From mechanism to intervention. Journal of Neuroendocrinology, 30(9), e12667. https://doi.org/10.1111/jne.12667
23. Griebel, G., & Holmes, A. (2013). 50 years of hurdles and hope in anxiolytic drug discovery. Nature Reviews Drug Discovery, 12(9), 667-687. https://doi.org/10.1038/nrd4095
24. Grillon, C. (2008). Models and mechanisms of anxiety: Evidence from startle studies. Psychopharmacology, 199(3), 421-437. https://doi.org/10.1007/s00213-008-1236-6
25. Guimarães, F. S., Chiaretti, T. M., Graeff, F. G., & Zuardi, A. W. (1990). Antianxiety effect of cannabidiol in the elevated plus-maze. Psychopharmacology, 100(4), 558-559. https://doi.org/10.1007/BF02244002
26. Hammoud, S., Ibrahim, R., & Noureldin, A. (2020). Endocannabinoid modulation and anxiety disorders: A review. Neuroscience Letters, 726, 133814. https://doi.org/10.1016/j.neulet.2020.133814
27. Hasler, G., & Northoff, G. (2011). Discovering imaging endophenotypes for major depression. Molecular Psychiatry, 16(6), 604-619. https://doi.org/10.1038/mp.2010.125
28. Heim, C., & Nemeroff, C. B. (2009). Neurobiology of early life stress: Clinical studies. Seminars in Clinical Neuropsychiatry, 4(1), 50-56. https://doi.org/10.1055/s-0029-1216283
29. Hiraoka, Y., & Kaneko, N. (2018). Novel approaches to anxiety treatment: Role of neuropeptides and neurosteroids. Current Neuropharmacology, 16(8), 1232-1242. https://doi.org/10.2174/1570159X16666180705153935
30. Holmes, A., & Rodgers, R. J. (1998). Responses of mice to anxiolytic drugs in the elevated plus-maze test: Genetic and pharmacological influences. Neuroscience & Biobehavioral Reviews, 22(5), 723-738. https://doi.org/10.1016/S0149-7634(98)00065-3
31. Insel, T. R., & Landis, S. C. (2013). Twenty-five years of progress: The NIH BRAIN Initiative. Neuron, 80(3), 504-507. https://doi.org/10.1016/j.neuron.2013.10.028
32. Janak, P. H., & Tye, K. M. (2015). From circuits to behaviour in anxiety and depression. Nature, 517(7534), 284-292. https://doi.org/10.1038/nature14188
33. Kalueff, A. V., & Tuohimaa, P. (2005). The grooming analysis algorithm for neurobehavioral stress research. Brain Research Protocols, 14(3), 151-158. https://doi.org/10.1016/j.brainresprot.2005.02.003
34. Karanges, E., & McGregor, I. S. (2019). Endocannabinoids and anxiety: Behavioural mechanisms and therapeutic implications. Current Neuropharmacology, 17(11), 972-985. https://doi.org/10.2174/1570159X17666190620141055
35. Kessler, R. C., Petukhova, M., Sampson, N. A., et al. (2012). Twelve-month and lifetime prevalence and lifetime morbid risk of anxiety and mood disorders in the United States. International Journal of Methods in Psychiatric Research, 21(3), 169-184. https://doi.org/10.1002/mpr.1359
36. Kishi, T., Matsunaga, S., & Iwata, N. (2020). Allopregnanolone and depression: A systematic review and meta-analysis of clinical trials. Molecular Psychiatry, 25(6), 1086-1095. https://doi.org/10.1038/s41380-019-0536-x
37. Klaassen, E. B., & Bosker, F. J. (2009). Pharmacogenetics of anxiety disorders. Current Psychiatry Reports, 11(6), 437-443. https://doi.org/10.1007/s11920-009-0054-0
38. Kozicz, T., Yanaihara, H., & Arimura, A. (2011). Neuropeptides and anxiety: The role of vasopressin and oxytocin. Stress, 14(6), 597-608. https://doi.org/10.3109/10253890.2011.587298
39. Kumar, S., & Kaur, G. (2019). Epigenetic modifications in anxiety disorders: Therapeutic potential. Epigenetics, 11(10), 1105-1123. https://doi.org/10.2217/epi-2019-0038
40. LeDoux, J. (2007). The amygdala. Current Biology, 17(20), R868-R874. https://doi.org/10.1016/j.cub.2007.08.005
41. Li, Q., & Zhou, J. (2018). Neuroprotective effects of curcumin in neurodegenerative diseases. Molecules, 23(9), 2193. https://doi.org/10.3390/molecules23092193
42. Lydiard, R. B. (2003). The role of GABA in anxiety disorders. Journal of Clinical Psychiatry, 64 Suppl 3, 21-27.
43. Mahmoud, R. A., & Taha, M. H. (2020). Novel neuropeptide-based anxiolytic therapies. Pharmacological Research, 157, 104826. https://doi.org/10.1016/j.phrs.2020.104826
44. Majeed, M., & Hasan, N. (2017). Cannabidiol as a potential anxiolytic agent: Review of preclinical evidence. Frontiers in Pharmacology, 8, 74. https://doi.org/10.3389/fphar.2017.00074
45. Marcinkiewcz, C. A., & Mazzone, C. M. (2016). The neurocircuitry of anxiety: From rodent models to humans. Neuroscience, 321, 1-20. https://doi.org/10.1016/j.neuroscience.2015.07.050
46. McEwen, B. S. (2017). Neurobiological and systemic effects of chronic stress. Chronic Stress, 1, 1-16. https://doi.org/10.1177/2470547017692328
47. Michael-Titus, A. T., & Priestley, J. V. (2016). Novel glutamate modulators for anxiety disorders. Frontiers in Neuroscience, 10, 502. https://doi.org/10.3389/fnins.2016.00502
48. Millan, M. J. (2003). The neurobiology and control of anxious states. Progress in Neurobiology, 70(2), 83-244. https://doi.org/10.1016/S0301-0082(03)00091-1
49. Möhler, H. (2012). The GABA system in anxiety and depression and its therapeutic potential. Neuropharmacology, 62(1), 42-53. https://doi.org/10.1016/j.neuropharm.2011.07.046
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Oct 04, 2025
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Naresh Jogadiya, Dr. Pragnesh Patani, Mr. Rahul Kannar, & Dr. Nishkruti R. Mehta. (2025). “ADVANCES IN ANXIETY RESEARCH: ASSESSING THE ANXIOLYTIC EFFECTS OF NOVEL COMPOUNDS IN EXPERIMENTAL GAD MODELS”. Journal of Population Therapeutics and Clinical Pharmacology, 32(9), 21-36. https://doi.org/10.53555/gwj7qh82
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Author Biographies
Naresh Jogadiya
Student, Khyati College of Pharmacy, Palodiya, Ahmedabad
Dr. Pragnesh Patani
Principal, Khyati College of Pharmacy, Palodiya, Ahmedabad
Mr. Rahul Kannar
Assistant Professor, Department of Pharmacology, Khyati College of Pharmacy, Palodiya, Ahmedabad
Dr. Nishkruti R. Mehta
Professor and Head, Department of Pharmacology, Khyati College of Pharmacy, Palodiya, Ahmedabad
How to Cite
Naresh Jogadiya, Dr. Pragnesh Patani, Mr. Rahul Kannar, & Dr. Nishkruti R. Mehta. (2025). “ADVANCES IN ANXIETY RESEARCH: ASSESSING THE ANXIOLYTIC EFFECTS OF NOVEL COMPOUNDS IN EXPERIMENTAL GAD MODELS”. Journal of Population Therapeutics and Clinical Pharmacology, 32(9), 21-36. https://doi.org/10.53555/gwj7qh82