The Effect of Long-Term Pregabalin Administration on Memory of Rat in Object Recognition Task

Document Type : Original Article (s)

Authors

1 Assistant Professor, Department of Pharmacology and Toxicology, School of Pharmacy and Pharmaceutical Sciences, Isfahan University of Medical Sciences, Isfahan, Iran

2 Professor, Department of Pharmacology and Toxicology, School of Pharmacy and Pharmaceutical Sciences, Isfahan University of Medical Sciences, Isfahan, Iran

3 Student of Pharmacy, Department of Pharmacology and Toxicology, School of Pharmacy and Pharmaceutical Sciences, Isfahan University of Medical Sciences, Isfahan, Iran

Abstract

Background: Pregabalin is used as an adjunctive therapy in partial seizure, fibromyalgia, neuropathic pain, and generalized anxiety disorders. This study was designed to determine the effects of pregabalin on memory of rat using object recognition task (ORT) method.Methods: Male wistar rats were divided into 4 groups (n = 7), and were injected 10, 30, or 100 mg/kg/day of pregabalin or normal saline for 28 days. For evaluation of memory, animals underwent ORT during two 3-minute trials with an one-hour interval to explore similar and similar or different objects. For this reason, the discrimination (d2) and recognition (R) indices, as well as the frequency of new object exploration (f), were compared in the second period of exposure (T2). The P-values of less than 0.05 were considered as statistically significant.Findings: Administration of pregabalin with the dose of 10, 30, or 100 mg/kg/day for 28 days significantly reduced the d2 (P < 0.050, P < 0.010, and P < 0.001, respectively) and R (P < 0.010, P < 0.001, and P < 0.001, respectively) indices, and frequency of exploration (P < 0.050, P < 0.050, and P < 0.001, respectively) in the T2 trials compared to the control group. 100 mg/kg of pregabalin showed more decrease in these factors compared to the dose of 10 mg/kg (P < 0.050, P < 0.001, and P < 0.050, respectively).Conclusion: The findings of this study indicate that long-term administration of different doses of pregabalin disrupts cognitive memory to new object in rats. The memory decline follows a dose-dependent pattern.

Keywords


  1. French JA, Kugler AR, Robbins JL, Knapp LE, Garofalo EA. Dose-response trial of pregabalin adjunctive therapy in patients with partial seizures. Neurology 2003; 60(10): 1631-7.
  2. Taylor CP, Angelotti T, Fauman E. Pharmacology and mechanism of action of pregabalin: The calcium channel α 2–δ (alpha 2–delta) subunit as a target for antiepileptic drug discovery. Epilepsy Res 2007; 73(2): 137-50.
  3. Dworkin RH, Kirkpatrick P. Pregabalin. Nat Rev Drug Discov 2005; 4(6): 455-6.
  4. Frampton JE, Scott LJ. Pregabalin: in the treatment of painful diabetic peripheral neuropathy. Drugs 2004; 64(24): 2813-20.
  5. Gatti A, Sabato AF, Occhioni R, Colini BG, Reale C. Controlled-release oxycodone and pregabalin in the treatment of neuropathic pain: results of a multicenter Italian study. Eur Neurol 2009; 61(3): 129-37.
  6. Richter RW, Portenoy R, Sharma U, Lamoreaux L, Bockbrader H, Knapp LE. Relief of painful diabetic peripheral neuropathy with pregabalin: a randomized, placebo-controlled trial. J Pain 2005; 6(4): 253-60.
  7. Arnold LM, Russell IJ, Diri EW, Duan WR, Young JP, Sharma U, et al. A 14-week, randomized, double-blinded, placebo-controlled monotherapy trial of pregabalin in patients with fibromyalgia. J Pain 2008; 9(9): 792-805.
  8. Belliotti TR, Capiris T, Ekhato IV, Kinsora JJ, Field MJ, Heffner TG, et al. Structure-activity relationships of pregabalin and analogues that target the alpha
  9. (2)-delta protein. J Med Chem 2005; 48(7): 2294-307.
  10. Sills GJ. The mechanisms of action of gabapentin and pregabalin. Curr Opin Pharmacol 2006; 6(1): 108-13.
  11. Kenney JW, Gould TJ. Modulation of hippocampus-dependent learning and synaptic plasticity by nicotine. Mol Neurobiol 2008; 38(1): 101-21.
  12. Salih L, Al-Mahdawi F, Al-Salihi A. Teratological effect of pregabalin drug on the prenatal development of the cerebellum in the albino rats. International Journal of Recent Scientific Research 2013; 5(7): 1381-5.
  13. Mack ML, Love BC, Preston AR. Building concepts one episode at a time: The hippocampus and concept formation. Neurosci Lett 2018; 680: 31-8.
  14. Yang T, Bavley RL, Fomalont K, Blomstrom KJ, Mitz AR, Turchi J, et al. Contributions of the hippocampus and entorhinal cortex to rapid visuomotor learning in rhesus monkeys. Hippocampus 2014; 24(9): 1102-11.
  15. Bateson AN. Further potential of the GABA receptor in the treatment of insomnia. Sleep Medicine 2006; 7: S3-S9.
  16. Majewska MD. Neuronal actions of dehydroepiandrosterone. Possible roles in brain development, aging, memory, and affect. Ann N Y Acad Sci 1995; 774: 111-20.
  17. White KG, Harper DN, Watson JE. Effects of chronic phenobarbital administration on forgetting functions in pigeons. Pharmacol Biochem Behav 1994; 49(2): 427-31.
  18. Camfield CS, Chaplin S, Doyle AB, Shapiro SH, Cummings C, Camfield PR. Side effects of phenobarbital in toddlers; behavioral and cognitive aspects. J Pediatr 1979; 95(3): 361-5.
  19. Salinsky M, Storzbach D, Munoz S. Cognitive effects of pregabalin in healthy volunteers: a double-blind, placebo-controlled trial. Neurology 2010; 74(9): 755-61.
  20. Kumar N, Laferriere A, Yu JS, Leavitt A, Coderre TJ. Evidence that pregabalin reduces neuropathic pain by inhibiting the spinal release of glutamate. J Neurochem 2010; 113(2): 552-61.
  21. Yokoyama T, Maeda Y, Audette KM, Sluka KA. Pregabalin reduces muscle and cutaneous hyperalgesia in two models of chronic muscle pain in rats. J Pain 2007; 8(5): 422-9.
  22. Brayfield A. Martindale: The complete drug reference. 38th ed. London, UK: Pharmaceutical Press; 2014. p. 545-7.
  23. Klaassen C. Casarett and Doull's toxicology: The basic science of poisons. 8th ed. New York, NY: McGraw-Hill Education; 2013. p. 32.
  24. Hosseini-Sharifabad A, Rabbani M, Sharifzadeh M, Bagheri N. Acute and chronic tramadol administration impair spatial memory in rat. Res Pharm Sci 2016; 11(1): 49-57.
  25. Akkerman S, Blokland A, Reneerkens O, van Goethem NP, Bollen E, Gijselaers HJ, et al. Object recognition testing: methodological considerations on exploration and discrimination measures. Behav Brain Res 2012; 232(2): 335-47.
  26. Akkerman S, Prickaerts J, Steinbusch HW, Blokland A. Object recognition testing: statistical considerations. Behav Brain Res 2012; 232(2): 317-22.
  27. Bergin PS, Thompson PJ, Baxendale SA, Fish DR, Shorvon SD. Remote memory in epilepsy. Epilepsia 2000; 41(2): 231-9.
  28. West PJ, Saunders GW, Remigio GJ, Wilcox KS, White HS. Antiseizure drugs differentially modulate theta-burst induced long-term potentiation in C57BL/6 mice. Epilepsia 2014; 55(2): 214-23.
  29. Park SP, Kwon SH. Cognitive effects of antiepileptic drugs. J Clin Neurol 2008; 4(3): 99-106.
  30. Dooley DJ, Donovan CM, Pugsley TA. Stimulus-dependent modulation of [(3)H]norepinephrine release from rat neocortical slices by gabapentin and pregabalin. J Pharmacol Exp Ther 2000; 295(3): 1086-93.
  31. Borroni AM, Fichtenholtz H, Woodside BL, Teyler TJ. Role of voltage-dependent calcium channel long-term potentiation (LTP) and NMDA LTP in spatial memory. J Neurosci 2000; 20(24): 9272-6.
  32. Van Harreveld A, Fifkova E. Involvement of glutamate in memory formation. Brain Res 1974; 81(3): 455-67.
  33. Riedel G, Platt B, Micheau J. Glutamate receptor function in learning and memory. Behav Brain Res 2003; 140(1-2): 1-47.
  34. McEntee WJ, Crook TH. Glutamate: its role in learning, memory, and the aging brain. Psychopharmacology (Berl) 1993; 111(4): 391-401.
  35. Klinkenberg I, Sambeth A, Blokland A. Acetylcholine and attention. Behav Brain Res 2011; 221(2): 430-42.
  36. Warburton EC, Koder T, Cho K, Massey PV, Duguid G, Barker GR, et al. Cholinergic neurotransmission is essential for perirhinal cortical plasticity and recognition memory. Neuron 2003; 38(6): 987-96.
  37. Hindmarch I, Trick L, Ridout F. A double-blind, placebo- and positive-internal-controlled (alprazolam) investigation of the cognitive and psychomotor profile of pregabalin in healthy volunteers. Psychopharmacology (Berl) 2005; 183(2): 133-43.
  38. Liliana MT, Lacramioara O, Catalina EL, Andra Sabina NV, Gabriela R, Gratiela P. The effects of pregabalin on psycho-motor abilities and cognitive processes in mice. Rev Med Chir Soc Med Nat Iasi 2015; 119(1): 185-92.
  39. Salat K, Gdula-Argasinska J, Malikowska N, Podkowa A, Lipkowska A, Librowski T. Effect of pregabalin on contextual memory deficits and inflammatory state-related protein expression in streptozotocin-induced diabetic mice. Naunyn Schmiedebergs Arch Pharmacol 2016; 389(6): 613-23.