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Effects of single and combined gabapentin use in elevated plus maze and forced swimming tests

Published online by Cambridge University Press:  30 July 2014

Fatma Sultan Kilic ,
Sule Ismailoglu ,
Bilgin Kaygisiz  and
Setenay Oner
Fatma Sultan Kilic*
Affiliation:
Department of Pharmacology, Medical Faculty, Eskisehir Osmangazi University, Eskisehir, Turkey
Sule Ismailoglu
Affiliation:
Department of Pharmacology, Medical Faculty, Eskisehir Osmangazi University, Eskisehir, Turkey
Bilgin Kaygisiz
Affiliation:
Department of Pharmacology, Medical Faculty, Eskisehir Osmangazi University, Eskisehir, Turkey
Setenay Oner
Affiliation:
Department of Biostatistics, Medical Faculty, Eskisehir Osmangazi University, Eskisehir, Turkey
*
Prof. Dr. Fatma Sultan Kilic, Eskisehir Osmangazi University, Medical Faculty, Department of Pharmacology, Meselik, Eskisehir, Turkey. Tel: +0 222 239 2979/4564; Fax: +90 222 239 3772; E-mail: [email protected]
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Abstract

Background

Gabapentin, a third-generation antiepileptic drug, is a structural analogue of γ-aminobutyric acid, which is an important mediator of central nervous system. There is clinical data indicating its effectiveness in the treatment of psychiatric illnesses such as bipolar disorder and anxiety disorders.

Objectives

We aimed to investigate the antidepressant and anxiolytic-like effects and mechanisms of gabapentin in rats.

Material and Methods

Female Spraque–Dawley rats weighing 250±20 g were used. A total of 13 groups were formed, each containing 8 rats: gabapentin (5, 10, 20, 40 mg/kg), amitriptyline (10 mg/kg), sertraline (5 mg/kg), diazepam (5 mg/kg), ketamine (10 mg/kg), gabapentin 20 mg/kg was also combined with amitriptyline (10 mg/kg), sertraline (5 mg/kg), diazepam (5 mg/kg) and ketamine (10 mg/kg). All the drugs were used intraperitoneally as single dose. Saline was administered to the control group. Elevated plus maze and forced swimming tests were used as experimental models of anxiety and depression, respectively.

Results

It was observed that gabapentin showed an anxiolytic-like and antidepressant-like effect in all doses in rats. Its antidepressant effect was found to be the same as the antidepressant effects of amitriptyline and sertraline. There was no change in the antidepressant effect when gabapentin was combined with amitriptyline and ketamine, but there was an increase when combined with sertraline and diazepam. Gabapentin and amitriptyline showed similar anxiolytic effect, whereas ketamine and diazepam had more potent anxiolytic effect compared with them.

Conclusions

These data suggest that gabapentin may possess antidepressant- and anxiolytic-like effects.

Keywords

antidepressantanxiolyticelevated plus mazeforced swimming testgabapentin
Type
Original Articles
Information
Acta Neuropsychiatrica , Volume 26 , Issue 5 , October 2014 , pp. 307 - 314
Copyright
© Scandinavian College of Neuropsychopharmacology 2014 

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References

1.Karataş, G, Tamam, L, Ozpoyraz, N. Gabapentin in the treatment of anxiety disorders. Bull Clin Psychopharmacol 2003;13:37–42.Google Scholar
2.Young, LT, Robb, JC, Hasey, GMet al.Gabapentin as an adjunctive treatment in bipolar disorder. J Affect Disord 1999;55:73–77.Google Scholar
3.Egashira, T, Inoue, T, Shirai, Y, Iwata, K, Honma, J, Koyama, T. Adjunctive gabapentin for treatment-resistant insomnia of bipolar disorder: a case report. Clin Neuropharmacol 2011;34:129–130.Google Scholar
4.Wettermark, B, Brandt, L, Kieler, H, Bodén, R. Pregabalin is increasingly prescribed for neuropathic pain, generalised anxiety disorder and epilepsy but many patients discontinue treatment. Int J Clin Pract 2014;68:104–110.Google Scholar
5.Darbà, J, Kaskens, L, Pérez, C, Álvarez, E, Navarro-Artieda, R, Sicras-Mainar, A. Pharmacoeconomic outcomes for pregabalin: a systematic review in neuropathic pain, generalized anxiety disorder, and epilepsy from a Spanish perspective. Adv Ther 2014;31:1–29.Google Scholar
6.Tassone, DM, Boyce, E, Guyer, J, Nuzum, D. Pregabalin: a novel gamma-aminobutyric acid analogue in the treatment of neuropathic pain, partial-onset seizures, and anxiety disorders. Clin Ther 2007;29:26–48.CrossRefGoogle ScholarPubMed
7.Calza, A, Sogliani, C, Santoru, Fet al.Neonatal exposure to estradiol in rats influences neuroactive steroid concentrations, GABAA receptor expression, and behavioral sensitivity to anxiolytic drugs. J Neurochem 2010;113:1285–1295.CrossRefGoogle ScholarPubMed
8.Smith, SS. α4βδ GABAA receptors and tonic inhibitory current during adolescence: effects on mood and synaptic plasticity. Front Neural Circuits 2013;7:135.CrossRefGoogle ScholarPubMed
9.Gulinello, M, Gong, QH, Smith, SS. Progesterone withdrawal increases the anxiolytic actions of gaboxadol: role of α4βδ GABAA receptors. Neuroreport 2003;14:43–46.CrossRefGoogle Scholar
10.de-Paris, F, Sant’Anna, MK, Vianna, MRet al.Effects of gabapentin on anxiety induced by simulated public speaking. J Psychopharmacol 2003;17:184–188.Google ScholarPubMed
11.Kulkarni, SK, Singh, K, Bishnoi, M. Comparative behavioural profile of newer antianxiety drugs on different mazes. Indian J Exp Biol 2008;46:633–638.Google ScholarPubMed
12.de-Paris, F, Busnello, JV, Vianna, MRet al.The anticonvulsant compound gabapentin possesses anxiolytic but not amnesic effects in rats. Behav Pharmacol 2000;11:169–173.Google Scholar
13.Valente, MM, Bortolotto, V, Cuccurazzu, Bet al.α2δ ligands act as positive modulators of adult hippocampal neurogenesis and prevent depression-like behavior induced by chronic restraint stress. Mol Pharmacol 2012;82:271–280.Google Scholar
14.Pellow, S, Chopin, P, File, SE, Briley, M. Validation of open: closed arm entries in an elevated plus-maze as a measure of anxiety in the rat. J Neurosci Methods 1985;14:149–167.Google Scholar
15.Porsolt, RD, Anton, G, Blavet, N, Jalfre, M. Behavioural despair in rats: a new model sensitive to antidepressant treatments. Eur J Pharmacol 1978;47:379–391.CrossRefGoogle ScholarPubMed
16.Pollack, MH, Matthews, J, Scott, EL. Gabapentin as a potential treatment for anxiety disorders. Am J Psychiatry 1998;155:992–993.Google Scholar
17.Foye, W. Central nervous system depressants: sedative-hypnotics, benzodiazepines. In: William O. Foye, editor. Principles of Medicinal Chemistry, 3rd edn. Pennsylvania, PA: Lea and Febiger, 1989. p. 165–166.Google Scholar
18.Kayaalp, O. Antiepileptik İlaçlar. In: Rasyonel Tedavi Yönünden Tıbbi Farmakoloji, vol. 2. Ankara, 2009. p. 884–901.Google Scholar
19.Gilman, GA, Goodman, S, Rail, T, Mured, F. Goodman and Gilman’s The Pharmacological Basis of Therapeutics. USA: McGraw-Hill, 2006; p. 339–351.Google Scholar
20.Patty, F, Trivedi, MH, Fulton, M, Rush, AJ. Benzodiazepines as antidepressant: does GABA play a role in depression? Biol Psychiatry 1995;38:578–591.CrossRefGoogle Scholar
21.Furukawa, TA, Streiner, D, Young, LT, Kinosta, Y. Antidepressant plus benzodiazepine for major depression. Cochrane Database Syst Rev 2000;4:CD001026.Google Scholar
22.Feighner, JP. Overview of antidepressants currently used to treat anxiety disorders. J Clin Psychiatry 1999;60:18–22.Google ScholarPubMed
23.Parra, A, Everss, E, Monleon, S, Vinader-Caerols, C, Arenas, MC. Effects of acute amitriptyline administration on memory, anxiety and activity in male and female mice. Neurosci Res Commun 2002;31:135–144.CrossRefGoogle Scholar
24.Everss, E, Arenas, MC, Vinader-Caerols, C, Monleon, S, Parra, A. Piracetam counteracts the effects of amitriptyline on inhibitory avoidance in CD1 mice. Behav Brain Res 2005;159:235–242.CrossRefGoogle ScholarPubMed
25.Weinstock, M, Poltyrev, V, Bejar, C, Youdim, MB. Effect of TV3326, a novel monoamine-oxidase cholinesterase inhibitor, in rats models of anxiety and depression. Psychopharmacology 2002;160:318–324.CrossRefGoogle ScholarPubMed
26.Bilkei-Gorzo, A, Gyertyan, I, Levay, G. mCPP-induced anxiety in the light-dark box in rats: a new method for screening anxiolytic activity. Psychopharmacology (Berl) 1998;136:291–298.CrossRefGoogle ScholarPubMed
27.Bodnoff, SR, Suranyi-Cadotte, B, Quirion, R, Meaney, MJ. A comparison of the effects of diazepam versus several typical and atypical antidepressant drugs in an animal model of anxiety. Psychopharmacology (Berl) 1989;97:277–279.Google Scholar
28.Bodnoff, SR, Suranyi-Cadotte, B, Aitken, DH, Meaney, MJ. The effects of chronic antidepressant treatment in an animal model of anxiety. Psychopharmacology (Berl) 1998;95:298–302.Google Scholar
29.Askin, R, Turan, M, Cilli, AS, Kaya, N. Clomipramine versus sertraline in the treatment of obsessive compulsive disorder. Eur Neuropsychopharmacol 1997;7:228–229.CrossRefGoogle Scholar
30.Rao, D, Tovar, M, Oseroff, SBet al.Crystal-field and exchange interactions of dilute Gd+3 ions in Eu2CuO4. Phys Rev B Condens Matter 1988;38:8920–8922.Google Scholar
31.Javitt, DC. Glutamate as a therapeutic target in psychiatric disorders. Mol Psychiatry 2004;9:984–997.CrossRefGoogle ScholarPubMed
32.Krystal, JH, D’Souza, DC, Petrakis, ILet al.NMDA agonists and antagonists as probes of glutamatergic dsyfunction and pharmacotherapies in neuropsychiatric disorders. Harv Rev Psychiatry 1999;7:125–143.Google Scholar
33.Vizi, ES. Role of high-affinity receptors and membrane transporters in nonsynaptic communication and drug action in central nervous system. Pharmacol Rev 2000;52:63–90.Google Scholar
34.Engin, E, Treit, D, Dickson, CT. Anxiolytic and antidepressant-like properties of ketamine in behavioral and neurophysiological animal models. Neuroscience 2009;161:359–369.CrossRefGoogle ScholarPubMed
35.Engin, E, Treit, D, Dickson, CT. Corrigendum to ‘anxiolytic- and antidepressant-like properties of ketamine in behavioral and neurophysiological animal models’. Neuroscience 2009;162:1438–1439.Google Scholar
36.Maeng, S, Carlos, A, Zarate, JRet al.Cellular mechanisms underlying the antidepressant effects of ketamine: role of α-amino-3hydroxy-5-methylisoxazole-4-propionic acid receptors. Biol Psychiatry 2008;63:349–352.Google Scholar
37.Pirrenger, C, Sanacora, G, Krystal, JH. The NMDA receptor as a therapeutic target in major depressive disorders. CNS Neurol Disord Drug Targets 2007;6:101–115.Google Scholar
38.Phelps, LE, Brutsche, N, Moral, JR. Family history of alcohol dependence and initial antidepressant response to an NMDA antagonist. Biol Psychiatry 2008;65:181–184.CrossRefGoogle Scholar