Skip to content
2000
image of The Neuroprotective Action of Resveratrol Against Cognitive Impairments Induced by Lorazepam in Male Rats

Abstract

Introduction/Aim

The study examines how chronic resveratrol administration affects behavioral and neurochemical changes caused by Lorazepam (LZP), a classical anti-anxiety medicine associated with neurodegenerative and neurological problems.

Method

Forty male rats were placed into four groups: a control group receiving 1% Tween 80, the LZP group receiving 2 mg/kg/day, the Resveratrol group receiving 50 mg/kg/day, and the LZP plus resveratrol group receiving the same doses of LZP and Resveratrol. Oral therapy was given daily for 6 weeks. The animals were euthanized after open field and Y maze behavioral tests. In specific brain regions, neurochemical analyses were performed on GABA, glutamic acid, monoamines (norepinephrine, dopamine, and serotonin) and their metabolites, DNA fragmentation (8-hydroxy-2–deoxyguanosine or 8-HdG), brain-derived neurotrophic factor (BDNF), and Ca-ATPase.

Results

Resveratrol therapy improved GABA, glutamic acid, monoamines, and their metabolites in the cerebral cortex, hippocampus, and striatum. Additionally, it reduced DNA fragmentation (8-HdG) and counteracted LZP-induced Ca-ATPase downregulation at a significant level ( 0.05). Resveratrol also reversed LZP-induced behavioral changes in the Y maze and open field tests.

Conclusion

Resveratrol has anxiolytic-like actions like benzodiazepines and neuroprotective capabilities against LZP-induced adverse effects.

Loading

Article metrics loading...

/content/journals/cds/10.2174/0115748863312358240919103439
2024-10-09
2025-01-27
Loading full text...

Full text loading...

References

  1. Mikulecká A. Šubrt M. Pařízková M. Mareš P. Kubová H. Consequences of early postnatal benzodiazepines exposure in rats. II. Social behavior. Front. Behav. Neurosci. 2014 8 169 10.3389/fnbeh.2014.00169 24982619
    [Google Scholar]
  2. Goddard A.W. Mason G.F. Appel M. Rothman D.L. Gueorguieva R. Behar K.L. Krystal J.H. Krystal J.H. Impaired GABA neuronal response to acute benzodiazepine administration in panic disorder. Am. J. Psychiatry 2004 161 12 2186 2193 10.1176/appi.ajp.161.12.2186 15569888
    [Google Scholar]
  3. Morishita S. Clonazepam as a therapeutic adjunct to improve the management of depression: A brief review. Hum. Psychopharmacol. 2009 24 3 191 198 10.1002/hup.1015 19330803
    [Google Scholar]
  4. Cunha-Oliveira T. Rego A.C. Garrido J. Borges F. Macedo T. Oliveira C.R. Neurotoxicity of heroin–cocaine combinations in rat cortical neurons. Toxicology 2010 276 1 11 17 10.1016/j.tox.2010.06.009 20600547
    [Google Scholar]
  5. Baselt R.C. Disposition of toxic drugs and chemicals in man. 8th ed Foster City, CA Biomedical Publications 2008
    [Google Scholar]
  6. Longo L.P. Johnson B. Addiction: Part I. Benzodiazepines--side effects, abuse risk and alternatives. Am. Fam. Physician 2000 61 7 2121 2128 10779253
    [Google Scholar]
  7. Steentoft A. Linnet K. Blood concentrations of clonazepam and 7-aminoclonazepam in forensic cases in Denmark for the period 2002–2007. Forensic Sci. Int. 2009 184 1-3 74 79 10.1016/j.forsciint.2008.12.004 19150586
    [Google Scholar]
  8. Wilms H. Claasen J. Röhl C. Sievers J. Deuschl G. Lucius R. Involvement of benzodiazepine receptors in neuroinflammatory and neurodegenerative diseases: Evidence from activated microglial cells in vitro. Neurobiol. Dis. 2003 14 3 417 424 10.1016/j.nbd.2003.07.002 14678758
    [Google Scholar]
  9. Takaoka M. Resveratrol, a new phenolic compound, from Veratrum grandiflorum. J. Chem. Soc. Jpn. 1939 60 1090 1100
    [Google Scholar]
  10. Aggarwal B.B. Shishodia S.S. Resveratrol in Health and Disease. New York Marcel Dekker, Inc. 2006
    [Google Scholar]
  11. Slattery D.A. Desrayaud S. Cryan J.F. GABAB receptor antagonist-mediated antidepressant-like behavior is serotonin-dependent. J. Pharmacol. Exp. Ther. 2005 312 1 290 296 10.1124/jpet.104.073536 15333677
    [Google Scholar]
  12. Socała K. Nieoczym D. Pieróg M. Wyska E. Szafarz M. Doboszewska U. Wlaź P. Effect of tadalafil on seizure threshold and activityof antiepileptic drugs in three acute seizure tests in mice. Neurotox. Res. 2018 34 3 333 346 10.1007/s12640‑018‑9876‑4 29427285
    [Google Scholar]
  13. El Khashab I.H. Abdelsalam R.M. Elbrairy A.I. Attia A.S. Chrysin attenuates global cerebral ischemic reperfusion injury via suppression of oxidative stress, inflammation and apoptosis. Biomed. Pharmacother. 2019 112 108619 10.1016/j.biopha.2019.108619 30797156
    [Google Scholar]
  14. Reagan-Shaw S. Nihal M. Ahmad N. Dose translation from animal to human studies revisited. FASEB J. 2008 22 3 659 661 10.1096/fj.07‑9574LSF 17942826
    [Google Scholar]
  15. Pagel P. Blome J. Wolf H.U. High-performance liquid chromatographic separation and measurement of various biogenic compounds possibly involved in the pathomechanism of Parkinson’s disease. J. Chromatogr., Biomed. Appl. 2000 746 2 297 304 10.1016/S0378‑4347(00)00348‑0 11076082
    [Google Scholar]
  16. Lodovici M. Casalini C. Briani C. Dolara P. Oxidative liver DNA damage in rats treated with pesticide mixtures. Toxicology 1997 117 1 55 60 10.1016/S0300‑483X(96)03553‑6 9020199
    [Google Scholar]
  17. Roghani M. Joghataie M.T. Jalali M.R. Baluchnejadmojarad T. Time course of changes in passive avoidance and Y – Maze performance in male diabetic rats. Iran. Biomed. J. 2006 10 2 99 104
    [Google Scholar]
  18. Griffin C.E. III Kaye A.M. Bueno F.R. Kaye A.D. Benzodiazepine pharmacology and central nervous system-mediated effects. Ochsner J. 2013 13 2 214 223 23789008
    [Google Scholar]
  19. Wang H. Hui K.M. Chen Y. Xu S. Wong J.T.F. Xue H. Structure-activity relationships of flavonoids, isolated from Scutellaria baicalensis, binding to benzodiazepine site of GABA(A) receptor complex. Planta Med. 2002 68 12 1059 1062 10.1055/s‑2002‑36357 12494329
    [Google Scholar]
  20. Cueto-Escobedo J. Andrade-Soto J. Lima-Maximino M. Maximino C. Hernández-López F. Rodríguez-Landa J.F. Involvement of GABAergic system in the antidepressant-like effects of chrysin (5,7-dihydroxyflavone) in ovariectomized rats in the forced swim test: Comparison with neurosteroids. Behav. Brain Res. 2020 386 112590 10.1016/j.bbr.2020.112590 32184157
    [Google Scholar]
  21. Majewska M.D. Harrison N.L. Schwartz R.D. Barker J.L. Paul S.M. Steroid hormone metabolites are barbiturate-like modulators of the GABA receptor. Science 1986 232 4753 1004 1007 10.1126/science.2422758 2422758
    [Google Scholar]
  22. Uren A.G. Wong L. Pakusch M. Fowler K.J. Burrows F.J. Vaux D.L. Choo K.H.A. Survivin and the inner centromere protein INCENP show similar cell-cycle localization and gene knockout phenotype. Curr. Biol. 2000 10 21 1319 1328 10.1016/S0960‑9822(00)00769‑7 11084331
    [Google Scholar]
  23. Huopaniemi L. Keist R. Randolph A. Certa U. Rudolph U. Diazepam‐induced adaptive plasticity revealed by α1 GABA A receptor‐specific expression profiling. J. Neurochem. 2004 88 5 1059 1067 10.1046/j.1471‑4159.2003.02216.x 15009662
    [Google Scholar]
  24. Mata A.M. Berrocal M. Sepúlveda M.R. Impairment of the activity of the plasma membrane Ca2+-ATPase in Alzheimer’s disease. Biochem. Soc. Trans. 2011 39 3 819 822 10.1042/BST0390819 21599654
    [Google Scholar]
  25. Li R. Zang A. Zhang L. Zhang H. Zhao L. Qi Z. Wang H. Chrysin ameliorates diabetes-associated cognitive deficits in Wistar rats. Neurol. Sci. 2014 35 10 1527 1532 10.1007/s10072‑014‑1784‑7 24737349
    [Google Scholar]
  26. Yang C. Hu Y.M. Zhou Z.Q. Zhang G.F. Yang J.J. Acute administration of ketamine in rats increases hippocampal BDNF and mTOR levels during forced swimming test. Ups. J. Med. Sci. 2013 118 1 3 8 10.3109/03009734.2012.724118 22970723
    [Google Scholar]
/content/journals/cds/10.2174/0115748863312358240919103439
Loading
/content/journals/cds/10.2174/0115748863312358240919103439
Loading

Data & Media loading...


  • Article Type:
    Research Article
Keywords: cognitive deficits ; resveratrol ; neurobehavior ; Lorazepam ; neuroprotection ; neurotransmitters
This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error
Please enter a valid_number test