Neuroscience Letters 492 (2011) 124–128 Contents lists available at ScienceDirect Neuroscience Letters journal homepage: www.elsevier.com/locate/neulet Gabapentin, A GABA analogue, enhances cognitive performance in mice Ipek Komsuoglu Celikyurt ∗ , Oguz Mutlu, Guner Ulak, Furuzan Yildiz Akar, Faruk Erden Kocaeli University, Department of Pharmacology, Faculty of Medicine, Psychopharmacology Laboratory, 41380, Kocaeli, Umuttepe, Turkey article info Article history: Received 10 December 2010 Received in revised form 16 January 2011 Accepted 27 January 2011 Keywords: Morris water maze Passive avoidance Modified elevated plus maze Gabapentin Mice Memory abstract Gabapentin is one of the new antiepileptic drugs (AEDs) launched recently. The advantage of new AEDs includes newer mechanism of action, broad spectrum of antiseizure effects, lesser drug interactions and fewer side effects. Gabapentin (GBP) a GABA analogue, is efficacious in several neurological and psychiatric conditions and it is conventionally used in the treatment of partial epilepsies. In this study, we aimed to evaluate the effects of GBP on learning and memory processes of naive mice in Morris water maze (MWM), passive avoidance (PA) and modified elevated plus maze (mEPM) tests. GBP (5 and 10 mg/kg, i.p.) was administered on the probe trial of MWM and on the acquisation session of PA and mEPM tests. In the MWM test, GBP (10 mg/kg) significantly increased the time spent in target quadrant and GBP (5 and 10 mg/kg) significantly decreased the distance to platform compared to control group. In the mEPM test, GBP (5 and 10 mg/kg) significantly decreased the transfer latency compared to control group on the second day and in the PA test, GBP (5 and 10 mg/kg) significantly prolonged retention latency compared to control group. Our results indicate that GBP has improving effects on spatial and emotional cognitive performance of naive mice in MWM, PA and mEPM tasks. © 2011 Elsevier Ireland Ltd. All rights reserved. Antiepileptic drugs (AEDs) are a major treatment consideration for patients with epilepsy. The main concern in choosing an appropri- ate antiepileptic is efficient control of seizures. The most prevalent of the cognitive side effects observed in an antiepileptic drug therapy in clinical use are sedation, sommolence, distractibility, insomnia and diziness. Gabapentin, (1-(aminonomethy) cyclohexaneatic acid) (GBP), a GABA analogue was originally developed for the treatment of epilepsy and is widely used to relieve neuropathic pain [18]. It is also efficacious in migraine, tremor, social phobia and bipolar disor- der [26]. GBP prevents seizures in a wide variety of animal models including generalized tonic-clonic and partial seizures [23] and cur- rently in clinical use in patients with partial seizures resistant to other AEDs [11]. GBP prevents pain responses in several animal models of hyper- algesia and prevents neuronal death in vitro and in vivo by models of neurodegenerative disease like amyotrophic lateral sclerosis. Although GBP may have several different pharmacological actions, modulation of GABA and glutamate synthesis may also appear to be important [23]. Cognitive effects of GBP and other AEDs have been compared in a number of clinical studies. GBP as add-on treatment has been shown to have favorable effects on cognition in clinical studies in humans. In a doubleblind, add-on, crossover study of 27 patients ∗ Corresponding author. Tel.: +90 262 303 71 02; fax: +90 262 303 80 03. E-mail address: ikomsu@hotmail.com (I.K. Celikyurt). with refractory partial seizures, it is reported that GBP has no neg- ative side effects on cognition except for an increase in drowsiness at 2400 mg/day but not at lower doses [9]. Cognitive side effects associated with old antiepileptics are moderate and can frequently be clinically significant. In a double-blind, randomized, crossover study comparing GBP to car- bamazepine (CBZ) in healthy adults with 5 weeks treatment arms found statistically better performance for GBP, but none for CBZ [13]. In contrast, a 12-week, randomized, double-blind, parallel-group study of CBZ and GBP in healthy volunteers using quantitated EEG and a cognitive battery found no significant dif- ferences between CBZ and GBP [19]. In a randomized double blind triple crossover study in patients with complex partial epilepsy, there is no cognitive differences found between carbamazepine and phenytoin, and phenobarbital produces greater cognitive differ- ences than the two other drugs [12]. In a double-blind, randomized, placebo-controlled parallel study in healthy volunteers, the effects of topiramate and GBP on cognitive abilities were evaluated and GBP was significantly better than topiramate on 50% of the 24 vari- ables [20]. Cognitive effects of first and second generation AEDs and com- parative studies for the effects of them were also performed in animal models. It is reported that valproic acid reduces spatial working memory and cell proliferation in the hippocampus [27] and valproate administered after traumatic brain injury provides neuroprotection and improves cognitive function in rats [7]. In a study, the effect of carbamazepine and lamotrigine on cognitive function and oxidative stress in brain during chemical epilepto- 0304-3940/$ – see front matter © 2011 Elsevier Ireland Ltd. All rights reserved. doi:10.1016/j.neulet.2011.01.072