Effect of gabapentin on haloperidol induced inhibition of conditioned avoidance response in rat

Authors

  • Nishant B. Bhansali Department of Pharmacology, M P Shah Medical College, Jamnagar - 361008, India
  • Yash N. Goyal Research Scientist, Torrent Pharmaceuticals, Ahmedabad, India
  • Baluswamy Divakar Department of Pharmacology, Government Medical College, Surat, India
  • Sureshchandra D. Mistry Department of Pharmacology, GMERS Medical College, Valsad, India
  • Dinesh A. Chavda Department of Pharmacology, M P Shah Medical College, Jamnagar - 361008, India
  • Jiyo Chacko Department of Pharmacology, M P Shah Medical College, Jamnagar - 361008, India

Keywords:

Acquisition response, conditioned-avoidance response, gabapentin, haloperidol, Rat

Abstract

Background: Haloperidol, an antipsychotic adversely affects acquisition and retention of a learned task. We decided to test the effect of Gabapentin, a new anti-epileptic drug using conditioned avoidance response model with cook’s pole climbing apparatus and haloperidol.

Methods: Four groups of six rats were taken for this purpose. All the rats were first given drugs for five days and then trained for a period of 15 days. Gabapentin was given in a dose of 100mg/kg intra peritoneal, while haloperidol was given 0.5mg/kg intra peritoneal.

Results: At the end of the training duration rats in the vehicle and gabapentin treated group achieved ≥85% acquisition responses. While the haloperidol and haloperidol + gabapentin group did not achieve the desired percentage of learning. A learning curve was plotted by using the percentage of conditioned responses in each group versus number of days. The mean ± SD percentage of conditioned responses of day 14 and 15 were for haloperidol group 26.19 ±11.90, for vehicle group 86.90 ± 4.29, for the gabapentin treated group 95.24 ± 2.38 and for the gabapentin + haloperidol group 46.42 ± 12.20. These figures and the learning curve suggest that gabapentin treated rats had a better acquisition response and haloperidol depressed learning.

Conclusions: At the end of study duration we found that gabapentin significantly improved the acquisition response than the vehicle control group. Also haloperidol depressed the acquisition response. Gabapentin did not lead to reversal of haloperidol induced depression of acquisition process.

References

Wadenberg ML. Conditioned avoidance response in the development of new antipsychotics. Curr Pharm Des 2010;16:358-70.

Natesan S, Reckless GE, Nobrega JN, Fletcher PJ, Kapur S. Dissociation between in vivo occupancy and functional antagonism of dopamine D2 receptors: comparing aripiprazole to other antipsychotics in animal models. Neuropsychopharmacology 2006;31:1854-63.

Telgedy G, Fekete M, Balazs M, Kadar T. Effect of a new antidepressant drug on active avoidance behavior in rats. Comparative study with tricyclic antidepressants. Arch Int Pharmacodyn Ther 1983;226:50-9.

Saha N, Datta H, Sharma PL. Effects of morphine, buprenorphine, pentazocine and nalorphine on acquisition and extinction of active avoidance response in rats. Indian J Physiol Pharmacol 1990;34:179-82.

Li M, He W, Mead A. Olanzapine and risperidone disrupt conditioned avoidance responding in phencyclidine or amphetamine pretreated rats by selectively weakening motivational salience of conditioned stimulus. Behav Pharmacol 2009;20:84-98.

Lazarova-Bakarova MB, Petkova BP, Todorov IK, Petkov VD. Memory impairment induced by combined disturbance of noradrenergic and dopaminergic neurotransmission: effect of nootropic drugs. Acta Physiol Pharmacol Bulg 1991;17:29-34.

Rosenberg JM, Harrell C, Ristic H, Werner RA, de Rosayro AM. The effect of gabapentin on neuropathic pain. Clin J Pain 1997;13:251-5.

Young LT, Robb JC, Hasey GM, MacQueen GM, Patelis Siotis I, Marriott M, Joffe RT. Gabapentin as an adjunctive treatment in bipolar disorder. J Affect Disord 1999;55:73-7.

Taylor CP. Mechanisms of action of gabapentin. Rev Neurol (Paris) 1997;153 Suppl 1:S39-45.

Blake MG, Boccia MM, Acosta GB, Baratti CM. Posttraining administration of pentylenetetrazol dissociates gabapentin effects on memory consolidation from that on memory retrieval process in mice. Neurosci Lett 2004;368:211-5.

Boccia, MM, Kopf, SR, Baratti, CM. The enhancement of retention performance induced by picrotoxin in mice may be mediated through a release of endogenous vasopressin. Behav Pharmacol 1996;7:254-60.

Umathe SN, Wanjari MM, Manna SS, Jain NS. A possible participation of gonadotropin-releasing hormone in the neuroleptic and cataleptic effect of haloperidol. Neuropeptides 2009;43:251-7.

Ghosh MN. Fundamentals of experimental pharmacology. 5th edition, Kolkata: Hilton & Company; 2011.

Spear NE, Miller JS, Jagielo JA. Animal memory and learning. Ann Rev Psychol 1990;41:169-211.

Monti JM, Ruiz M. Increased disrupting effects of haloperidol on a conditioned avoidance response after 6-hydroxydopamine treatment. Pharmacol Biochem Behav 1975;3:943-5.

Yonko DI. Possible role of brain dopaminergic system in the memory effects of central stimulants. Methods Find Exp Clin Pharmacol 1984;6:235-9.

Ichihara K, Nabeshima T, Kameyama T. Opposite effects induced by low and high doses of apomorphine on single-trial passive avoidance learning in mice. Pharmacol Biochem Behav 1988;30:107-13.

Ichihara K, Nabeshima, T, Kameyama T. Effect of haloperidol, sulpiride and SCH 23390 on passive avoidance learning in mice. Eur J Pharmacol 1988;151:435-42.

Taghzouti K, Garrgues AM, Labouesse J, Moal M LE, Simon H. Bovine serum albumin - haloperidol and neurochemical effects following a single injection in nucleus accumbens. Life Sci 1987;40:127-37.

Dougherty JA, Rhoney DH. Gabapentin: a unique anti-epileptic agent. Neurol Res 2001; 23:821-9.

Dimond KR, Pande AC, Lamoreus L, Pierce MW. Effect of gabapentin (Neurontin) on mood and well-being in patients with epilepsy. Prog Neuropsycho pharmacol Biol Psychiatry 1996;20:407-17.

Harden CL, Pick LH. Alterations in mood and anxiety in epilepsy patients treated with gabapentin (Abstract). Epilepsia 1996;37(suppl):137.

Mortimore CM, Trimble M, Emmers E. Effect of gabapentin on cognition and quality of life in patients with epilepsy. Seizure 1998;7:359-64.

Dodrill CB, Arnett JL, Hayes AG, Garofalo EA, Greeley CA, Greiner MJ. Cognitive abilities and adjustment with gabapentin: results of a multisite study. Epilepsy Res 1999;35:109-21.

Pande AC, Davidson JR, Jefferson JW, Janney CA, Katzelnick DJ, Weisler RH, et al. Treatment of social phobia with gabapentin: a placebo-controlled study. J Clin Psychopharmacol 1999;19:341-8.

Shannon HE, Love PL. Effects of antiepileptic drugs on working memory as assessed by spatial alternation performance in rats. Epilepsy Behav 2004;5:857-65.

Acosta GB, Boccia MM, Baratti CM. Gabapentin, an antiepileptic drug, improves memory storage in mice. Neurosci Lett 2000;279:173-6.

Brioni JD. Role of GABA during the multiple consolidation of memory. Drug Develop Res 1993;28:3-27.

Brioni JD, McGaugh JL. Post-training administration of GABAergic antagonists enhances retention of aversively motivated tasks. Psychopharmacology (Berl) 1988;96:505-10.

Czubak A, Nowakowska E, Kus K, Sadowski C, Matschay A. Effect of gabapentin on cognitive processes in rats not exposed and exposed to tobacco smoke during fetal life. Hum Exp Toxicol 2008;27:883-94.

Downloads

Published

2017-02-04

How to Cite

Bhansali, N. B., Goyal, Y. N., Divakar, B., Mistry, S. D., Chavda, D. A., & Chacko, J. (2017). Effect of gabapentin on haloperidol induced inhibition of conditioned avoidance response in rat. International Journal of Basic & Clinical Pharmacology, 1(3), 216–220. Retrieved from https://www.ijbcp.com/index.php/ijbcp/article/view/1430

Issue

Section

Original Research Articles