Comparative effects of chronic administrations of gabapentin, pregabalin and baclofen on rat memory using object recognition test

Asma Salimzade Salimzade, Ali Hosseini-Sharifabad, Mohammad Rabbani

Abstract


Memory impairment is one of the greatest concerns when it comes to long-term CNS-affecting drug administration. Drugs like gabapentin, pregabalin and baclofen are administered in a long-term period in conditions such as epilepsy, neuropathic pain, spasticity associated with spinal cord injury or multiple sclerosis. Despite their wide spread use, few data are available on the effects of these drugs on cognitive functions, such as learning memory. In the present study, the effects of long-term administration of gabapentin, pregabalin and baclofen on memory were investigated in a comparative manner. Male Wistar rats received intraperitoneal (i.p.) injection of gabapentin (30 mg/kg), pregabalin (30 mg/kg), baclofen               (3 mg/kg), combination of gabapentin/baclofen (30/3 mg/kg) and combination of pregabalin/baclofen (30/3 mg/kg) once a day for 3 weeks respective to their groups. After the end of treatments, rat memories were assessed using the object-recognition task. The discrimination and recognition indices (RI and DI) in the T2 trials were used as the memory indicating factors. The results showed that daily i.p. administrations of pregabalin but not gabapentin or baclofen significantly decreased DI and RI compared to saline group. In combination groups, either gabapentin or pregabalin impaired discrimination between new and familiar objects. Our findings suggested that pregabalin alone or in combination with baclofen significantly caused cognitive deficits.


Keywords


Gabapentin; Pregabalin; Baclofen; Object recognition task; Memory; Chronic

Full Text:

PDF

References


Finnerup NB, Attal N, Haroutounian S, McNicol E, Baron R, Dworkin RH, et al. Pharmacotherapy for neuropathic pain in adults: a systematic review and meta-analysis. The Lancet Neurol. 2015;14(2):162-173.

Jensen TS, Baron R, Haanpää M, Kalso E, Loeser JD, Rice AS, et al. A new definition of neuropathic pain. Pain. 2011;152(10):2204-2205.

Jensen TS. Anticonvulsants in neuropathic pain: rationale and clinical evidence. Eur J Pain. 2002;6(Suppl A):61-68.

Hanna M, O'Brien C, Wilson MC. Prolonged‐release oxycodone enhances the effects of existing gabapentin therapy in painful diabetic neuropathy patients. Eur J Pain. 2008;12(6):804-813.

Ivanhoe CB, Reistetter TA. Spasticity: the misunderstood part of the upper motor neuron syndrome. Am J Phys Med Rehabil. 2004;83(10):S3-S9.

Vinik A. Use of antiepileptic drugs in the treatment of chronic painful diabetic neuropathy. J Clin Endocrin Metab. 2005;90(8):4936-4945.

Lind G, Meyerson BA, Winter J, Linderoth B. Intrathecal baclofen as adjuvant therapy to enhance the effect of spinal cord stimulation in neuropathic pain: a pilot study. Eur J Pain. 2004;8(4):377-383.

Lind G, Schechtmann G, Winter J, Meyerson BA, Linderoth B. Baclofen‐enhanced spinal cord stimulation and intrathecal baclofen alone for neuropathic pain: Long‐term outcome of a pilot study. Eur J Pain. 2008;12(1):132136.

Rabchevsky AG, Patel SP, Lyttle TS, Eldahan KC, O’Dell CR, Zhang Y, et al. Effects of gabapentin on muscle spasticity and both induced as well as spontaneous autonomic dysreflexia after complete spinal cord injury. Front Physiol. 2012; 3:329.

Taylor CP. Mechanisms of analgesia by gabapentin and pregabalin–calcium channel α2‐δ [Cav α2‐δ] ligands. Pain. 2009;142(1-2):13-16.

Cheng JK, Chen CC, Yang JR, Chiou LC. The antiallodynic action target of intrathecal gabapentin: Ca2+ channels, KATP channels or N-methyl-d-aspartic acid receptors? Anesthesia and analgesia. 2006;102(1):182-187.

Micheva KD, Taylor CP, Smith SJ. Pregabalin reduces the release of synaptic vesicles from cultured hippocampal neurons. Mol Pharmacol. 2006;70(2):467-476.

Tassone DM, Boyce E, Guyer J, Nuzum D. Pregabalin: a novel γ-aminobutyric acid analogue in the treatment of neuropathic pain, partial-onset seizures, and anxiety disorders. Clin Ther. 2007;29(1):26-48.

Meyerson BA, Linderoth B. Mode of action of spinal cord stimulation in neuropathic pain. J Pain Symptom Manage. 2006;31(4):S6-S12.

Saulino M, Burton A, Danyo D, Frost S, Glanzer J, Solanki D. Intrathecal ziconotide and baclofen provide pain relief in seven patients with neuropathic pain and spasticity: case reports. Eur J Phys Rehabil Med. 2009;45(1):61-67.

Meador KJ. Cognitive and memory effects of the new antiepileptic drugs. Epilepsy Res. 2006;68(1):63-67.

Mula M, Trimble MR. Antiepileptic drug-induced cognitive adverse effects. CNS drugs. 2009;23(2):121-137.

Kim D-H, Ryu J-H. Differential effects of scopolamine on memory processes in the object recognition test and the Morris water maze test in mice. Biomol Ther. 2008;16(3):173-178.

Gregoire S, Michaud V, Chapuy E, Eschalier A, Ardid D. Study of emotional and cognitive impairments in mononeuropathic rats: effect of duloxetine and gabapentin. Pain. 2012;153(8):1657-1663.

Baastrup C, Jensen TS, Finnerup NB. Pregabalin attenuates place escape/avoidance behavior in a rat model of spinal cord injury. Brain Res. 2011;1370:129-135.

McNamara RK, Skelton RW. Baclofen, a selective GABAB receptor agonist, dose-dependently impairs spatial learning in rats. Pharmacol Biochem Behav. 1996;53(2):303-308.

Ennaceur A, Neave N, Aggleton JP. Spontaneous object recognition and object location memory in rats: the effects of lesions in the cingulate cortices, the medial prefrontal cortex, the cingulum bundle and the fornix. Exp Brain Res. 1997;113(3):509-519.

Antunes M, Biala G. The novel object recognition memory: neurobiology, test procedure, and its modifications. Cogn Process. 2012;13(2):93-110.

Zarrindast MR, Bakhsha A, Rostami P, Shafaghi B. Effects of intrahippocampal injection of GABAergic drugs on memory retention of passive avoidance learning in rats. J Psychopharmacol. 2002;16(4):313-3139.

Motamedi GK, Meador KJ. Antiepileptic drugs and memory. Epilepsy Behav. 2004;5(4):435-439.

Leach JP, Girvan J, Paul A, Brodie MJ. Gabapentin and cognition: a double blind, dose ranging, placebo controlled study in refractory epilepsy. J Neurol Neurosurg Psychiatry . 1997;62(4):372-376.

Mortimore C, Trimble M, Emmers E. Effects of gabapentin on cognition and quality of life in patients with epilepsy. Seizure. 1998;7(5):359-364.

Martin R, Kuzniecky R, Ho S, Hetherington H, Pan J, Sinclair K, et al. Cognitive effects of topiramate, gabapentin, and lamotrigine in healthy young adults. Neurology. 1999;52(2):321-327.

Ortinski P, Meador KJ. Cognitive side effects of antiepileptic drugs. Epilepsy Behav. 2004;5:60-65.

Salinsky M, Storzbach D, Spencer D, Oken B, Landry T, Dodrill C. Effects of topiramate and gabapentin on cognitive abilities in healthy volunteers. Neurology. 2005;64(5):792-798.

Chavant F, Favrelière S, Lafay‐Chebassier C, Plazanet C, Pérault‐Pochat MC. Memory disorders associated with consumption of drugs: updating through a case/noncase study in the French PharmacoVigilance Database. Br J Clin Pharmacol. 2011;72(6):898-904.

Salinsky M, Storzbach D, Munoz S. Cognitive effects of pregabalin in healthy volunteers A double-blind, placebo-controlled trial. Neurology. 2010;74(9):755-761.

Mohan AJ, Krishna K, Jisham K, Mehdi S, Nidavani RB. Protective effect of tulsi and levetiracetam on memory impairment induced by pregabalin on mice. IOSR J Pharm Biol Sci. 2014;9:46-52.

Ciesielski A-S, Samson S, Steinhoff BJ. Neuropsychological and psychiatric impact of add-on titration of pregabalin versus levetiracetam: a comparative short-term study. Epilepsy Behav. 2006;9(3):424-431.

McClelland D, Evans RM, Barkworth L, Martin DJ, Scott RH. A study comparing the actions of gabapentin and pregabalin on the electrophysiological properties of cultured DRG neurones from neonatal rats. BMC Pharmacol. 2004;4:14.

Bockbrader HN, Wesche D, Miller R, Chapel S, Janiczek N, Burger P. A comparison of the pharmacokinetics and pharmacodynamics of pregabalin and gabapentin. Clin Pharmacokinet. 2010;49(10):661-669.

Browning KN, Travagli RA. Mechanism of action of baclofen in rat dorsal motor nucleus of the vagus. Am J Physiol Gastrointest Liver Physiol. 2001;280(6):G1106-G1113.

Levin ED, Weber E, Icenogle L. Baclofen interactions with nicotine in rats: effects on memory. Pharmacol Biochem Behav. 2004;79(2):343-348.

Zarrindast MR, Khodjastehfar E, Oryan S, Torkaman-Boutorabi A. Baclofen-impairment of memory retention in rats: possible interaction with adrenoceptor mechanism(s). Eur J Pharmacol. 2001;411(3):283-288.

Thomas CK, Hager-Ross CK, Klein CS. Effects of baclofen on motor units paralysed by chronic cervical spinal cord injury. Brain. 2010;133 (Pt 1):117-125.


Refbacks

  • There are currently no refbacks.