Article Sidebar

Submitted
Apr 23, 2021
Published
Apr 23, 2021
Download
PDF
Statistic
Read Counter : 34 Download : 21

Main Article Content

Abstract

BACKGROUND AND OBJECTIVE


Anxiety that occurs during alcohol withdrawal may be the precipitating factor for relapse of alcoholism. Earlier studies have demonstrated calcium channel activity peaks during alcohol withdrawal and calcium channel antagonists were found to decrease behavioral manifestations of alcohol withdrawal syndrome. The objective of the study was to evaluate the anxiolytic potential of calcium channel antagonists, verapamil and nimodipine during ethanol withdrawal in rats.


METHODOLOGY


Male wistar albino rats were fed with 10% ethanol liquid diet for 4 weeks. Ethanol was withdrawn 8 hours before test procedure. Verapamil (20mg/kg) and nimodipine (10mg/kg) were administered orally. Elevated plus maze (EPM) and Open field test (OFT) were used to assess the anxiolytic activity.


RESULT


In the EPM model, the time spent in the open arm and closed arm was increased and decreased respectively in rats treated with both verapamil and nimodipine as compared to control. Number of rearing in open arm and closed arm were also increased which shows increased exploratory behavior in rats. In OFT model, the time spent in central squares and peripheral squares was increased and decreased respectively in rats treated with verapamil and nimodipine as compared to control. Number of entries into the central area and the number of lines crossed in central and peripheral areas were also increased in drug treated rats as compared to control. Number of rearing was significantly increased in the central areas but not in the peripheral areas.


CONCLUSION


Verapamil and Nimodipine significantly reduced ethanol withdrawal induced anxiety. Calcium channel antagonists could be effectively used as alternative to benzodiazepines in ethanol withdrawal induced anxiety.

Keywords

Verapamil Nimodipine Ethanol withdrawal Anxiety

Article Details

How to Cite
R. Saravanan, V. Venkataramanan, & G. Karthikeyan. (2021). Effect of verapamil and nimodipine in reversing the ethanol withdrawal induced anxiety in rats. International Journal of Research in Pharmacology & Pharmacotherapeutics, 4(3), 366-371. https://doi.org/10.61096/ijrpp.v4.iss3.2015.366-371
Download Citation
Endnote/Zotero/Mendeley (RIS)
BibTeX

References

  1. [1]. Lovinger DM, White G, Weight FF, 1989. Ethanol inhibits NMDA-activated ion current in hippocampal neurons. Science., 243(4899):1721-1724
  2. [2]. Ticku MK, Lowrimore P, Lehoullier P, 1986. Ethanol enhances GABA-induced 36Cl-influx in primary spinal cord cultured neurons. Brain Research Bulletin., 17:123-126
  3. [3]. Dildy-Mayfield J.E, Mihic S.J, Liu Y, Deitrich R.A, Harris R.A, 1992. Actions of long chain alcohols on GABA A and glutamate receptors: relation to in vivo effects. Br J Pharmacol., 118:378-384
  4. [4]. Grant AJ, Koski G, Treistman SN, 1993. Effect of chronic ethanol on calcium currents and calcium uptake in undifferentiated PC12 cells. Brain research., 600:280-284
  5. [5]. Dolin S, Little H, Hudspith M, Pagonis C, Littleton J, 1987. Increased dihydropyridine-sensitive calcium channels in rat brain may underlie ethanol physical dependence. Neuropharmacology., 26:275-279
  6. [6]. Messing RO, Carpenter CL, Diamond I, Greenberg DA, 1986. Ethanol regulates calcium channels in clonal neural cells. Proc. Natl. Acad. Sci. USA., 83:6213-15
  7. [7]. Koppi S, Eberhardt G, Haller R, König P, 1987. Calcium channel blocking agent in the treatment of acute alcohol withdrawal – caroverine versus meprobamate in a randomized double blind study. Neuropsychobiology., 17:49-52
  8. [8]. Bone GH, Majchrowicz E, Martin PR, Linnoila M, Nutt DJ, 1989. A comparison of calcium antagonists and diazepam in reducing ethanol withdrawal tremors. Psychopharmacology., 99:386-388
  9. [9]. Romach and Sellers, 1991. Management of the alcohol withdrawal syndrome. Annu Rev Med., 42:323-40.
  10. [10]. Daeppen JB, Gache P, Landry U, Sekera E, Schweizer V, Gloor S, et al. 2002. Symptom-triggered vs schedule fixed doses of benzodiazepine for alcohol withdrawal: a randomized treatment trial. Archives of internal medicine., 162:1117-1121
  11. [11]. Schuster CL and Humphries RH, 1981. Benzodiazepine dependency in alcoholics, Conn. Med., 1981 45:11
  12. [12]. O’brien CP 2005. Benzodiazepine use, abuse, and dependence. Jour. Clin. Psychiatry., 66(2):28-33
  13. [13]. Martijena ID, Lacerra C, Bustos SG, Molina VA, 2001. Chronic benzodiazepoine administration facilitates the subsequent development of ethanol dependence. Brain res., 891:236-246
  14. [14]. George KA and Dundee JW, 1977. Relative amnesic actions of diazepam, flunitrazepam and lorazepam in man. Br J Clin Pharmacol., 4(1):45-50
  15. [15]. Lister RG, 1985. The amnesic action of benzodiazepines in man. Neurosci Biobehav Rev. Spring., 9(1):87-94
  16. [16]. Heinala, Pieponen T and Heikkinen H, 1990. Diazepam loading in alcohol withdrawal: Clinical pharmacokinetics. International Journal of Clinical Pharmacology, Therapy and Toxicology., 28:211-217
  17. [17]. Littleton JM, Little HJ, Whittington MA, 1990. Effect of dihydropyridine calcium channel antagonists in ethanol withdrawal; doses required, stereo specificity and actions of BAY K8644. Psychopharmacology., 100(3):387-392
  18. [18]. Dolin SJ and Little HJ, 1989. Are changes in neuronal calcium channels involve in ethanol tolerance. J. Pharmaco. Exp. Ther.. 250:985-991
  19. [19]. Little HJ, Dolin SJ, Halsey MJ, 1986. Calcium channel antagonists also decrease the ethanol withdrawal syndrome. Life Sci., Dec 1;39 (22):2059-65
  20. [20]. Pellow S, Chopin P, File SE, Briley M, 1985. Validation of open:closed arm entries in elevated plus maze as a measure of anxiety in the rat. J Neurosci Methods., 14:149-67
  21. [21]. Handley SL and Mithani S, 1984. Effects of α-adrenoreceptor agonists and antagonists in a maze-exploration model of 'fear'-motivated behaviour. Naunyn- Schmeideberg's Arch Pharmacol., 327(1):1–5
  22. [22]. Rodgers RJ, Dalvi A 1997. Anxiety, defence and the elevated plus maze. Neurosci Biobehav Rev., 21(6): 801– 10
  23. [23]. Walf AA and Frye CA, 2007. The use of the elevated plus maze as an assay of anxiety-related behavior in rodents. Nat. Protoc., 2(2): 322 – 328
  24. [24]. Fernandez F, 2002. N/OFQ exerts anxiogenic actions in an open field. J Undergrad Res., 3:10
  25. [25]. Fernandes C and File SE, 1996. The influence of open arm ledges and maze experience in the elevated plus maze. Pharmacol. Biochem. Behave., 54:31-40
  26. [26]. Kokare DM, Chopde CT, Subhedar NK, 2006. Participation of alpha-melanocyte stimulating hormone in ethanol induced anxiolysis and withdrawal anxiety in rats. Neuropharmacology., 51(3):536-45
  27. [27]. Gatch MB, Wallis CJ, Lal H, 2000. Effects of ritanserin on ethanol withdrawal-induced anxiety in rats. Alcohol. 21(1):11-17.