Comparing the Efficacy of Escitalopram with and Without Crocin in Restoring I/O Functions and LTP Within the Hippocampal CA1 Region of Stressed Rats

Overview

Journal Adv Biomed Res

Specialty Biomedical Engineering

Date 2024 Dec 24

PMID 39717236

Authors

Mehran Joodaki

Maryam Radahmadi

Hojjatallah Alaei

Affiliations

Soon will be listed here.

Abstract

Background: Escitalopram, a pharmacological compound, and crocin, the active compound of saffron, influence brain functions and serotonin levels. This study examined the efficacy of escitalopram with and without crocin in restoring the input-output (I/O) functions and long-term potentiation (LTP) within the hippocampal cornu ammonis 1 (CA1) region of stressed rats.

Materials And Methods: Rats were divided into six groups: control (Co), sham (Sh), stress-recovery (St-Rec), stress-escitalopram (St-Esc), stress-crocin (St-Cr), and stress-escitalopram-crocin (St-Esc-Cr) groups. They underwent 14 days of restraint stress (6 h/day). After being subjected to stress, they received 14 days of escitalopram (20 mg/kg) and crocin (30 mg/kg), as well as co-administration of these two compounds during the next 14 days. The field excitatory postsynaptic potential (fEPSP) slope and amplitude were measured using I/O functions and LTP induction in the CA1 region. Corticosterone (CORT) levels were also evaluated.

Results: The fEPSPs slope and amplitude in the I/O functions and LTP induction significantly decreased in stressed rats without therapeutic intervention. These variables in the I/O functions declined in rats with escitalopram administration alone. All electrophysiological parameters showed an increase in rats treated with crocin alone compared to stressed subjects without any treatment. Serum CORT levels decreased only with crocin treatment for stressed rats.

Conclusion: Neural excitability and memory within the CA1 region were severely disrupted among stressed rats without any treatment. Furthermore, administering crocin alone improved neural excitability and memory post-chronic stress. Treatment with escitalopram alone also impaired neural excitability within the CA1 region. The use of escitalopram with and without crocin did not enhance memory under chronic stress.

References

McLaughlin K, Gomez J, Baran S, Conrad C . The effects of chronic stress on hippocampal morphology and function: an evaluation of chronic restraint paradigms. Brain Res. 2007; 1161:56-64. PMC: 2667378. DOI: 10.1016/j.brainres.2007.05.042. View

Sousa N, Lukoyanov N, Madeira M, Almeida O, Paula-Barbosa M . Reorganization of the morphology of hippocampal neurites and synapses after stress-induced damage correlates with behavioral improvement. Neuroscience. 2000; 97(2):253-66. DOI: 10.1016/s0306-4522(00)00050-6. View

Nawreen N, Baccei M, Herman J . Single Prolonged Stress Reduces Intrinsic Excitability and Excitatory Synaptic Drive Onto Pyramidal Neurons in the Infralimbic Prefrontal Cortex of Adult Male Rats. Front Cell Neurosci. 2021; 15:705660. PMC: 8342808. DOI: 10.3389/fncel.2021.705660. View

Hassani F, Naseri V, Razavi B, Mehri S, Abnous K, Hosseinzadeh H . Antidepressant effects of crocin and its effects on transcript and protein levels of CREB, BDNF, and VGF in rat hippocampus. Daru. 2014; 22(1):16. PMC: 3927874. DOI: 10.1186/2008-2231-22-16. View

Radahmadi M, Hosseini N, Alaei H . Effect of exercise, exercise withdrawal, and continued regular exercise on excitability and long-term potentiation in the dentate gyrus of hippocampus. Brain Res. 2016; 1653:8-13. DOI: 10.1016/j.brainres.2016.09.045. View

Jensen J, Gaarn Du Jardin K, Song D, Budac D, Smagin G, Sanchez C . Vortioxetine, but not escitalopram or duloxetine, reverses memory impairment induced by central 5-HT depletion in rats: evidence for direct 5-HT receptor modulation. Eur Neuropsychopharmacol. 2013; 24(1):148-59. DOI: 10.1016/j.euroneuro.2013.10.011. View

Tse Y, Lopez J, Moquin A, Wong S, Maysinger D, Wong T . The susceptibility to chronic social defeat stress is related to low hippocampal extrasynaptic NMDA receptor function. Neuropsychopharmacology. 2019; 44(7):1310-1318. PMC: 6785155. DOI: 10.1038/s41386-019-0325-8. View

Huang Y, Li D, Wang C, Sun N, Zhou W . Stachyose Alleviates Corticosterone-Induced Long-Term Potentiation Impairment the Gut-Brain Axis. Front Pharmacol. 2022; 13:799244. PMC: 8965576. DOI: 10.3389/fphar.2022.799244. View

Benatti C, Alboni S, Blom J, Mendlewicz J, Tascedda F, Brunello N . Molecular changes associated with escitalopram response in a stress-based model of depression. Psychoneuroendocrinology. 2017; 87:74-82. DOI: 10.1016/j.psyneuen.2017.10.011. View

10.

GRAY J, Rubin T, Hunter R, McEwen B . Hippocampal gene expression changes underlying stress sensitization and recovery. Mol Psychiatry. 2013; 19(11):1171-8. PMC: 4061278. DOI: 10.1038/mp.2013.175. View

11.

Kim E, Kim J . Neurocognitive effects of stress: a metaparadigm perspective. Mol Psychiatry. 2023; 28(7):2750-2763. PMC: 9909677. DOI: 10.1038/s41380-023-01986-4. View

12.

Dvojkovic A, Nikolac Perkovic M, Sagud M, Nedic Erjavec G, Mihaljevic Peles A, Strac D . Effect of vortioxetine vs. escitalopram on plasma BDNF and platelet serotonin in depressed patients. Prog Neuropsychopharmacol Biol Psychiatry. 2020; 105:110016. DOI: 10.1016/j.pnpbp.2020.110016. View

13.

Heine V, Maslam S, Zareno J, Joels M, Lucassen P . Suppressed proliferation and apoptotic changes in the rat dentate gyrus after acute and chronic stress are reversible. Eur J Neurosci. 2004; 19(1):131-44. DOI: 10.1046/j.1460-9568.2003.03100.x. View

14.

Zheng Y, Tian C, Dong L, Tian L, Glabonjat R, Xiong C . Effect of arsenic-containing hydrocarbon on the long-term potentiation at Schaffer Collateral-CA1 synapses from infantile male rat. Neurotoxicology. 2021; 84:198-207. DOI: 10.1016/j.neuro.2021.04.002. View

15.

Constable P, Al-Dasooqi D, Bruce R, Prem-Senthil M . A Review of Ocular Complications Associated with Medications Used for Anxiety, Depression, and Stress. Clin Optom (Auckl). 2022; 14:13-25. PMC: 8884704. DOI: 10.2147/OPTO.S355091. View

16.

Anacker C, Zunszain P, Carvalho L, Pariante C . The glucocorticoid receptor: pivot of depression and of antidepressant treatment?. Psychoneuroendocrinology. 2010; 36(3):415-25. PMC: 3513407. DOI: 10.1016/j.psyneuen.2010.03.007. View

17.

Dastgerdi H, Radahmadi M, Reisi P . Comparative study of the protective effects of crocin and exercise on long-term potentiation of CA1 in rats under chronic unpredictable stress. Life Sci. 2020; 256:118018. DOI: 10.1016/j.lfs.2020.118018. View

18.

Jacobsen J, Mork A . The effect of escitalopram, desipramine, electroconvulsive seizures and lithium on brain-derived neurotrophic factor mRNA and protein expression in the rat brain and the correlation to 5-HT and 5-HIAA levels. Brain Res. 2004; 1024(1-2):183-92. DOI: 10.1016/j.brainres.2004.07.065. View

19.

Vanicek T, Reed M, Seiger R, Godbersen G, Klobl M, Unterholzner J . Increased left dorsolateral prefrontal cortex density following escitalopram intake during relearning: a randomized, placebo-controlled trial in healthy humans. Ther Adv Psychopharmacol. 2022; 12:20451253221132085. PMC: 9677158. DOI: 10.1177/20451253221132085. View

20.

Hadipour M, Kaka G, Bahrami F, Meftahi G, Pirzad Jahromi G, Mohammadi A . Crocin improved amyloid beta induced long-term potentiation and memory deficits in the hippocampal CA1 neurons in freely moving rats. Synapse. 2018; 72(5):e22026. DOI: 10.1002/syn.22026. View