Abstract
Selective serotonin reuptake inhibitors (SSRIs) are widely used drugs for the treatment of depression. Citalopram is one of the most prescribed SSRIs that is useful for the treatment of depression, obsessive–compulsive disorder, and anxiety disorders. On the other hand, crocin (active constitute of saffron) has pro-cognitive and mood enhancer effects. Also, both citalopram and crocin affect the function and expression of brain-derived neurotrophic factor (BDNF) and synaptophysin, two molecular factors that are involved in cognitive functions and mood. In the present study, we aim to investigate the interaction effect of citalopram and crocin on rats’ performance in the open field test (locomotor activity and anxiety-like behavior) and the shuttle box (passive avoidance memory). Citalopram was injected at the doses of 10, 30, and 50 mg/kg, and crocin was injected at the dose of 50 mg/kg; all administrations were intraperitoneal. Real-time PCR was used to assess the expression level of BDNF and synaptophysin in the hippocampus. The results showed that citalopram (30 and 50 mg/kg) impaired passive avoidance memory and decreased BDNF and synaptophysin expression in the hippocampus, while crocin reversed memory impairment, and BDNF and synaptophysin expression in the hippocampus of rats received citalopram 30 mg/kg. Also, crocin partially showed these effects in rats that received citalopram 50 mg/kg. The results of the open field test were unchanged. In conclusion, we suggested that BDNF and synaptophysin may be involved in the effects of both citalopram and crocin.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
Data availability
Will be available upon a reasonable request.
References
Abbaszade-Cheragheali A, Beheshti F, Kakhki S, Khatibi SR, Dehnokhalaji F, Akbari E, Fathi H, Safari Farimani S (2022) Crocin, the main active saffron (Crocus sativus L.) constituent, as a potential candidate to prevent anxiety and depressive-like behaviors induced by unpredictable chronic mild stress. Neurosci Lett 791:136912. https://doi.org/10.1016/j.neulet.2022.136912
Abbaszade-Cheragheali A, Kakhki S, Khatibi SR, Hosseini M, Navari F, Beheshti F (2023) Feeding crocin ameliorate cognitive dysfunction, oxidative stress and neuroinflammation induced by unpredictable chronic mild stress in rats. Inflammopharmacology. https://doi.org/10.1007/s10787-023-01250-9
Aguilar-Martinez IS, Reyes-Mendez ME, Herrera-Zamora JM, Osuna-Lopez F, Virgen-Ortiz A, Mendoza-Munoz N, Gongora-Alfaro JL, Moreno-Galindo EG, Alamilla J (2020) Synergistic antidepressant-like effect of capsaicin and citalopram reduces the side effects of citalopram on anxiety and working memory in rats. Psychopharmacology 237(7):2173–2185. https://doi.org/10.1007/s00213-020-05528-6
Ahmed El-Sheikh A, AM H, Ali El-Kordy E, MA A, HR F, Mahmoud El-Sharaby R, SM S, AES A, HS R, ME A, Safwat El-Deeb O, Raafat Ibrahim R, AI H (2023) Crocin lessens desipramine-induced phospholipidosis biomarker levels via targeting oxidative stress- related PI3K/Akt/mTOR signaling pathways in the rat liver. Acta Biomed 94 (2):e2023141. https://doi.org/10.23750/abm.v94i2.14442
Appelberg B (2003) Long term citalopram prevents recurrent depression in the elderly and is well tolerated. Evid Based Ment Health 6(1):24. https://doi.org/10.1136/ebmh.6.1.24
Bekinschtein P, Cammarota M, Katche C, Slipczuk L, Rossato JI, Goldin A, Izquierdo I, Medina JH (2008) BDNF is essential to promote persistence of long-term memory storage. Proc Natl Acad Sci U S A 105(7):2711–2716. https://doi.org/10.1073/pnas.0711863105
Bjorkholm C, Monteggia LM (2016) BDNF - a key transducer of antidepressant effects. Neuropharmacology 102:72–79. https://doi.org/10.1016/j.neuropharm.2015.10.034
Bridoux A, Laloux C, Derambure P, Bordet R, Monaca Charley C (2013) The acute inhibition of rapid eye movement sleep by citalopram may impair spatial learning and passive avoidance in mice. J Neural Transm (vienna) 120(3):383–389. https://doi.org/10.1007/s00702-012-0901-0
Carboni L, Rullo L, Caputi FF, Stamatakos S, Candeletti S, Romualdi P (2022) Chronic trazodone and citalopram treatments increase trophic factor and circadian rhythm gene expression in rat brain regions relevant for antidepressant efficacy. Int J Mol Sci 23 (22). https://doi.org/10.3390/ijms232214041
Dorri SA, Hosseinzadeh H, Abnous K, Hasani FV, Robati RY, Razavi BM (2015) Involvement of brain-derived neurotrophic factor (BDNF) on malathion induced depressive-like behavior in subacute exposure and protective effects of crocin. Iran J Basic Med Sci 18(10):958–966
Du Y, Wang YL, Chen L, Li QE, Cheng Y (2023) Anti-depressant-like effects of rannasangpei and its active ingredient crocin-1 on chronic unpredictable mild stress mice. Front Pharmacol 14:1143286. https://doi.org/10.3389/fphar.2023.1143286
Eastwood SL, Burnet PW, Harrison PJ (1995) Altered synaptophysin expression as a marker of synaptic pathology in schizophrenia. Neuroscience 66(2):309–319. https://doi.org/10.1016/0306-4522(94)00586-t
Ebrahimi B, Vafaei S, Rastegar-Moghaddam SHR, Hosseini M, Tajik Yabr F, Mohammadipour A (2021) Crocin administration from childhood to adulthood increases hippocampal neurogenesis and synaptogenesis in male mice. J Kerman Univ Med Sci 28(3):243–251
Ennaceur A (2014) Tests of unconditioned anxiety - pitfalls and disappointments. Physiol Behav 135:55–71. https://doi.org/10.1016/j.physbeh.2014.05.032
Farhadi L, Hojati V, Khaksari M, Vaezi G (2022) Neuroprotective effects of crocin against ethanol neurotoxicity in the animal model of fetal alcohol spectrum disorders. Neurochem Res 47(4):1001–1011. https://doi.org/10.1007/s11064-021-03501-z
Feltmann K, Konradsson-Geuken A, De Bundel D, Lindskog M, Schilstrom B (2015) Antidepressant drugs specifically inhibiting noradrenaline reuptake enhance recognition memory in rats. Behav Neurosci 129(6):701–708. https://doi.org/10.1037/bne0000100
Garabadu D, Reddy BC, Krishnamurthy S (2015) Citalopram protects against cold-restraint stress-induced activation of brain-derived neurotrophic factor and expression of nuclear factor kappa-light-chain-enhancer of activated B cells in rats. J Mol Neurosci 55(2):355–366. https://doi.org/10.1007/s12031-014-0334-3
Ghadrdoost B, Vafaei AA, Rashidy-Pour A, Hajisoltani R, Bandegi AR, Motamedi F, Haghighi S, Sameni HR, Pahlvan S (2011) Protective effects of saffron extract and its active constituent crocin against oxidative stress and spatial learning and memory deficits induced by chronic stress in rats. Eur J Pharmacol 667(1–3):222–229. https://doi.org/10.1016/j.ejphar.2011.05.012
Ghalandari-Shamami M, Nourizade S, Yousefi B, Vafaei AA, Pakdel R, Rashidy-Pour A (2019) Beneficial effects of physical activity and crocin against adolescent stress induced anxiety or depressive-like symptoms and dendritic morphology remodeling in prefrontal cortex in adult male rats. Neurochem Res 44(4):917–929. https://doi.org/10.1007/s11064-019-02727-2
Ghalandari-Shamami M, Nourizade S, Barati M, Yousefi B, Pashayi M, Ali Vafaei A, Kokhaei P, Rashidy-Pour A (2021) Exercise and crocin prevent adolescent-stress induced impairment of spatial navigation and dendritic retraction in the hippocampal CA3 area in adult male rats. Brain Res 1754:147274. https://doi.org/10.1016/j.brainres.2020.147274
Gong WG, Wang YJ, Zhou H, Li XL, Bai F, Ren QG, Zhang ZJ (2017) Citalopram ameliorates synaptic plasticity deficits in different cognition-associated brain regions induced by social isolation in middle-aged rats. Mol Neurobiol 54(3):1927–1938. https://doi.org/10.1007/s12035-016-9781-x
Gudi V, Gai L, Herder V, Tejedor LS, Kipp M, Amor S, Suhs KW, Hansmann F, Beineke A, Baumgartner W, Stangel M, Skripuletz T (2017) Synaptophysin is a reliable marker for axonal damage. J Neuropathol Exp Neurol 76(2):109–125. https://doi.org/10.1093/jnen/nlw114
Heldt SA, Stanek L, Chhatwal JP, Ressler KJ (2007) Hippocampus-specific deletion of BDNF in adult mice impairs spatial memory and extinction of aversive memories. Mol Psychiatry 12(7):656–670. https://doi.org/10.1038/sj.mp.4001957
Horch HW, Katz LC (2002) BDNF release from single cells elicits local dendritic growth in nearby neurons. Nat Neurosci 5(11):1177–1184. https://doi.org/10.1038/nn927
Hosseini Dastgerdi A, Radahmadi M, Pourshanazari AA (2021) Comparing the effects of crocin at different doses on excitability and long-term potentiation in the CA1 area, as well as the electroencephalogram responses of rats under chronic stress. Metab Brain Dis 36(7):1879–1887. https://doi.org/10.1007/s11011-021-00747-y
Huang J, Xu Z, Chen H, Lin Y, Wei J, Wang S, Yu H, Huang S, Zhang Y, Li C, Zhou X (2022) Shen Qi Wan ameliorates learning and memory impairment induced by STZ in AD Rats through PI3K/AKT pathway. Brain Sci 12 (6). https://doi.org/10.3390/brainsci12060758
Hyttel J (1982) Citalopram–pharmacological profile of a specific serotonin uptake inhibitor with antidepressant activity. Prog Neuropsychopharmacol Biol Psychiatry 6(3):277–295. https://doi.org/10.1016/s0278-5846(82)80179-6
Ji ZH, Xu ZQ, Zhao H, Yu XY (2017) Neuroprotective effect and mechanism of daucosterol palmitate in ameliorating learning and memory impairment in a rat model of Alzheimer’s disease. Steroids 119:31–35. https://doi.org/10.1016/j.steroids.2017.01.003
Kamaei AK, Hosseini SF, Teimourparsaei P, Payamani M, Vaseghi S (2023) The effect of acute crocin on behavioral changes and BDNF expression level in socially isolated rats. Naunyn Schmiedebergs Arch Pharmacol. https://doi.org/10.1007/s00210-023-02843-5
Kesslak JP, So V, Choi J, Cotman CW, Gomez-Pinilla F (1998) Learning upregulates brain-derived neurotrophic factor messenger ribonucleic acid: a mechanism to facilitate encoding and circuit maintenance? Behav Neurosci 112(4):1012–1019. https://doi.org/10.1037//0735-7044.112.4.1012
Kukuia KKE, Burns FB, Adutwum-Ofosu KK, Appiah F, Amponsah SK, Begyinah R, Koomson AE, Ferka YT, Tagoe TA, Amoateng P (2023) Increased brain-derived neurotrophic factor and hippocampal dendritic spine density are associated with the rapid antidepressant-like effect of iron-citalopram and iron-imipramine combinations in mice. Neuroscience 519:90–106. https://doi.org/10.1016/j.neuroscience.2023.03.014
Li YC, Kavalali ET (2017) Synaptic vesicle-recycling machinery components as potential therapeutic targets. Pharmacol Rev 69(2):141–160. https://doi.org/10.1124/pr.116.013342
Liu R, Dang W, Jianting M, Su C, Wang H, Chen Y, Tan Q (2012) Citalopram alleviates chronic stress induced depression-like behaviors in rats by activating GSK3beta signaling in dorsal hippocampus. Brain Res 1467:10–17. https://doi.org/10.1016/j.brainres.2012.05.030
Liu C, Hao S, Zhu M, Wang Y, Zhang T, Yang Z (2018) Maternal separation induces different autophagic responses in the hippocampus and prefrontal cortex of adult rats. Neuroscience 374:287–294. https://doi.org/10.1016/j.neuroscience.2018.01.043
Liu J, Yang C, Yang J, Song X, Han W, Xie M, Cheng L, Xie L, Chen H, Jiang L (2019) Effects of early postnatal exposure to fine particulate matter on emotional and cognitive development and structural synaptic plasticity in immature and mature rats. Brain Behav 9(12):e01453. https://doi.org/10.1002/brb3.1453
Looti Bashiyan M, Nasehi M, Vaseghi S, Khalifeh S (2021) Investigating the effect of crocin on memory deficits induced by total sleep deprivation (TSD) with respect to the BDNF, TrkB and ERK levels in the hippocampus of male Wistar rats. J Psychopharmacol:2698811211000762. https://doi.org/10.1177/02698811211000762
Luo Y, Chaimani A, Kataoka Y, Ostinelli EG, Ogawa Y, Cipriani A, Salanti G, Furukawa TA (2018) Evidence synthesis, practice guidelines and real-world prescriptions of new generation antidepressants in the treatment of depression: a protocol for cumulative network meta-analyses and meta-epidemiological study. BMJ Open 8(12):e023222. https://doi.org/10.1136/bmjopen-2018-023222
Mahdavi MS, Nasehi M, Vaseghi S, Mousavi Z, Zarrindast MR (2021) The effect of alpha lipoic acid on passive avoidance and social interaction memory, pain perception, and locomotor activity in REM sleep-deprived rats. Pharmacol Rep 73(1):102–110. https://doi.org/10.1007/s43440-020-00161-8
Malboosi N, Nasehi M, Hashemi M, Vaseghi S, Zarrindast MR (2020) The neuroprotective effect of NeuroAid on morphine-induced amnesia with respect to the expression of TFAM, PGC-1alpha, DeltafosB and CART genes in the hippocampus of male Wistar rats. Gene 742:144601. https://doi.org/10.1016/j.gene.2020.144601
Miranda M, Morici JF, Zanoni MB, Bekinschtein P (2019) Brain-derived neurotrophic factor: a key molecule for memory in the healthy and the pathological brain. Front Cell Neurosci 13:363. https://doi.org/10.3389/fncel.2019.00363
Mohamadian M, Fallah H, Ghofrani-Jahromi Z, Rahimi-Danesh M, ShokouhiQareSaadlou MS, Vaseghi S (2023) Mood and behavior regulation: interaction of lithium and dopaminergic system. Naunyn Schmiedebergs Arch Pharmacol 396(7):1339–1359. https://doi.org/10.1007/s00210-023-02437-1
Morid OF, Menze ET, Tadros MG, George MY (2023) L-Carnitine modulates cognitive impairment induced by doxorubicin and cyclophosphamide in rats; insights to oxidative stress, inflammation, synaptic plasticity, liver/brain, and kidney/brain axes. J Neuroimmune Pharmacol. https://doi.org/10.1007/s11481-023-10062-1
Mutlu O, Ulak G, Celikyurt IK, Akar FY, Erden F (2011) Effects of citalopram on cognitive performance in passive avoidance, elevated plus-maze and three-panel runway tasks in naive rats. Chin J Physiol 54(1):36–46. https://doi.org/10.4077/cjp.2011.amk077
Navazani P, Vaseghi S, Hashemi M, Shafaati MR, Nasehi M (2021) Effects of treadmill exercise on the expression level of BAX, BAD, BCL-2, BCL-XL, TFAM, and PGC-1alpha in the hippocampus of thimerosal-treated rats. Neurotox Res 39(4):1274–1284. https://doi.org/10.1007/s12640-021-00370-w
Nie J, Zhang SY, Sun L, Qiu Q, Fang Y, Liu X, Li X (2020) Correlation between depressive behavior and expressions of S100beta and brain-derived neurotrophic factor in hippocampus and frontal cortex of rats. Zhongguo Yi Xue Ke Xue Yuan Xue Bao 42(2):209–215. https://doi.org/10.3881/j.issn.1000-503X.11306
Nikisch G, Mathe AA, Czernik A, Thiele J, Bohner J, Eap CB, Agren H, Baumann P (2005) Long-term citalopram administration reduces responsiveness of HPA axis in patients with major depression: relationship with S-citalopram concentrations in plasma and cerebrospinal fluid (CSF) and clinical response. Psychopharmacology 181(4):751–760. https://doi.org/10.1007/s00213-005-0034-3
National Research Council (US) Committee for the Update of the Guide for the Care and Use of Laboratory Animals (2011) Guide for the Care and Use of Laboratory Animals. 8th ed., National Academies Press (US). https://doi.org/10.17226/12910
Ott K, Heikkinen T, Lehtimaki KK, Paldanius K, Puolivali J, Pussinen R, Andriambeloson E, Huyard B, Wagner S, Schnack C, Wahler A, von Einem B, von Arnim CAF, Burmeister Y, Weyer K, Seilheimer B (2023) Vertigoheel promotes rodent cognitive performance in multiple memory tests. Front Neurosci 17:1183023. https://doi.org/10.3389/fnins.2023.1183023
Razavi BM, Sadeghi M, Abnous K, Vahdati Hasani F, Hosseinzadeh H (2017) Study of the role of CREB, BDNF, and VGF neuropeptide in long term antidepressant activity of crocin in the rat cerebellum. Iran J Pharm Res 16(4):1452–1462
Reddy AP, Sawant N, Morton H, Kshirsagar S, Bunquin LE, Yin X, Reddy PH (2021) Selective serotonin reuptake inhibitor citalopram ameliorates cognitive decline and protects against amyloid beta-induced mitochondrial dynamics, biogenesis, autophagy, mitophagy and synaptic toxicities in a mouse model of Alzheimer’s disease. Hum Mol Genet 30(9):789–810
Ren QG, Gong WG, Wang YJ, Zhou QD, Zhang ZJ (2015) Citalopram attenuates tau hyperphosphorylation and spatial memory deficit induced by social isolation rearing in middle-aged rats. J Mol Neurosci 56(1):145–153. https://doi.org/10.1007/s12031-014-0475-4
Rezaie M, Nasehi M, Vaseghi S, Alimohammadzadeh K, IslamiVaghar M, Mohammadi-Mahdiabadi-Hasani MH, Zarrindast MR (2021) The interaction effect of sleep deprivation and cannabinoid type 1 receptor in the CA1 hippocampal region on passive avoidance memory, depressive-like behavior and locomotor activity in rats. Behav Brain Res 396:112901. https://doi.org/10.1016/j.bbr.2020.112901
Schaefer TL, Grace CE, Braun AA, Amos-Kroohs RM, Graham DL, Skelton MR, Williams MT, Vorhees CV (2013) Cognitive impairments from developmental exposure to serotonergic drugs: citalopram and MDMA. Int J Neuropsychopharmacol 16(6):1383–1394. https://doi.org/10.1017/S1461145712001447
Schmitt K, Holsboer-Trachsler E, Eckert A (2016) BDNF in sleep, insomnia, and sleep deprivation. Ann Med 48(1–2):42–51. https://doi.org/10.3109/07853890.2015.1131327
Sharbaf Shoar N, Fariba KA, Padhy RK (2022) Citalopram. In: StatPearls. Treasure Island (FL),
Sharbaf Shoar N, Fariba KA, Padhy RK (2023) Citalopram. In: StatPearls. Treasure Island (FL) with ineligible companies. Disclosure: Kamron Fariba declares no relevant financial relationships with ineligible companies. Disclosure: Ranjit Padhy declares no relevant financial relationships with ineligible companies
Sharma R, Rahi S, Mehan S (2019) Neuroprotective potential of solanesol in intracerebroventricular propionic acid induced experimental model of autism: insights from behavioral and biochemical evidence. Toxicol Rep 6:1164–1175. https://doi.org/10.1016/j.toxrep.2019.10.019
Sprowles JL, Hufgard JR, Gutierrez A, Bailey RA, Jablonski SA, Williams MT, Vorhees CV (2016) Perinatal exposure to the selective serotonin reuptake inhibitor citalopram alters spatial learning and memory, anxiety, depression, and startle in Sprague-Dawley rats. Int J Dev Neurosci 54:39–52. https://doi.org/10.1016/j.ijdevneu.2016.08.007
Stanic D, Oved K, Israel-Elgali I, Jukic M, Batinic B, Puskas N, Shomron N, Gurwitz D, Pesic V (2021) Synergy of oxytocin and citalopram in modulating Itgb3/Chl1 interplay: relevance to sensitivity to SSRI therapy. Psychoneuroendocrinology 129:105234. https://doi.org/10.1016/j.psyneuen.2021.105234
Thiel G (1993) Synapsin I, synapsin II, and synaptophysin: marker proteins of synaptic vesicles. Brain Pathol 3(1):87–95. https://doi.org/10.1111/j.1750-3639.1993.tb00729.x
Vaseghi S, Mostafavijabbari A, Alizadeh MS, Ghaffarzadegan R, Kholghi G, Zarrindast MR (2023) Intricate role of sleep deprivation in modulating depression: focusing on BDNF, VEGF, serotonin, cortisol, and TNF-alpha. Metab Brain Dis 38(1):195–219. https://doi.org/10.1007/s11011-022-01124-z
Wang Y, Zhou S, Song X, Ding S, Wang B, Wen J, Chen C (2022) Study on antidepressant effect and mechanism of crocin mediated by the mTOR signaling pathway. Neurochem Res 47(10):3126–3136. https://doi.org/10.1007/s11064-022-03668-z
Yang J, Pei Y, Pan YL, Jia J, Shi C, Yu Y, Deng JH, Li B, Gong XL, Wang X, Wang XM, Ma X (2013) Enhanced antidepressant-like effects of electroacupuncture combined with citalopram in a rat model of depression. Evid Based Complement Alternat Med 2013:107380. https://doi.org/10.1155/2013/107380
Yoshimura R, Kishi T, Suzuki A, Umene-Nakano W, Ikenouchi-Sugita A, Hori H, Otani K, Iwata N, Nakamura J (2011) The brain-derived neurotrophic factor (BDNF) polymorphism Val66Met is associated with neither serum BDNF level nor response to selective serotonin reuptake inhibitors in depressed Japanese patients. Prog Neuropsychopharmacol Biol Psychiatry 35(4):1022–1025. https://doi.org/10.1016/j.pnpbp.2011.02.009
Yousefsani BS, Mehri S, Pourahmad J, Hosseinzadeh H (2021) Protective effect of crocin against mitochondrial damage and memory deficit induced by beta-amyloid in the hippocampus of rats. Iran J Pharm Res 20(2):79–94. https://doi.org/10.22037/ijpr.2020.112206.13604
Zhang L, Zhao Q, Chen CH, Qin QZ, Zhou Z, Yu ZP (2014) Synaptophysin and the dopaminergic system in hippocampus are involved in the protective effect of rutin against trimethyltin-induced learning and memory impairment. Nutr Neurosci 17(5):222–229. https://doi.org/10.1179/1476830513Y.0000000085
Zhang F, Zhu X, Yu P, Sheng T, Wang Y, Ye Y (2022a) Crocin ameliorates depressive-like behaviors induced by chronic restraint stress via the NAMPT-NAD(+)-SIRT1 pathway in mice. Neurochem Int 157:105343. https://doi.org/10.1016/j.neuint.2022.105343
Zhang X, Ni L, Hu S, Yue B, Chen X, Yuan D, Wang T, Zhou Z (2022b) Polygonatum sibiricum ameliorated cognitive impairment of naturally aging rats through BDNF-TrkB signaling pathway. J Food Biochem 46(12):e14510. https://doi.org/10.1111/jfbc.14510
Zhang Y, Du L, Yan J, Bai Q, Niu Q, Mo Y, Zhang Q, Nie J (2022c) Prenatal benzo[a]pyrene exposure impairs hippocampal synaptic plasticity and cognitive function in SD rat offspring during adolescence and adulthood via HDAC2-mediated histone deacetylation. Ecotoxicol Environ Saf 246:114180. https://doi.org/10.1016/j.ecoenv.2022.114180
Zhang J, Gao Q, Gao J, Lv L, Liu R, Wu Y, Li X, Jin Y, Wang L (2023) Moderate-intensity intermittent training alters the DNA methylation pattern of PDE4D gene in hippocampus to improve the ability of spatial learning and memory in aging rats reduced by D-galactose. Brain Sci 13 (3). https://doi.org/10.3390/brainsci13030422
Author information
Authors and Affiliations
Contributions
SN conducted the experiments. SHH analyzed data. SV wrote the manuscript, validation, design, and search. BGY supervised and designed the research process. All the authors approved the final version. The authors declare that all data were generated in-house and that no paper mill was used.
Corresponding author
Ethics declarations
Ethical approval
N/A.
Consent to participate
N/A.
Consent for publication
N/A.
Competing interests
The authors declare no competing interests.
Additional information
Publisher's Note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Rights and permissions
Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.
About this article
Cite this article
Nasseri, S., Hajrasouliha, S., Vaseghi, S. et al. Interaction effect of crocin and citalopram on memory and locomotor activity in rats: an insight into BDNF and synaptophysin levels in the hippocampus. Naunyn-Schmiedeberg's Arch Pharmacol (2024). https://doi.org/10.1007/s00210-024-03069-9
Received:
Accepted:
Published:
DOI: https://doi.org/10.1007/s00210-024-03069-9