Abstract

Background: Among the antiepileptic drugs, Phenobarbital (PB) has the highest potential for adverse effects on cognition and behavior. The memory formation process depends on the integrity of hippocampus neuronal circuits. This study aimed to determine the volumetric alterations of Dentate Gyrus (DG) and Cornu Ammonis of hippocampus following long-term administration of PB. Methods: 20 male Wistar rats were divided into four groups (control and 3 experimental groups). Control animals were received saline and experimental groups were received phenobarbital intraperitoneally at doses of 50, 75 and 100 mg/kg daily for 45 days. The posterior region of the brain (which contains hippocampus) was cut into serial 25 μm thick sections. Every 20th section was selected with systematic random sampling. The unbiased stereological Cavallieri method was used to determine the volume of the layers of hippocampal subfields. Findings: Our results showed the significant effect of PB on the volume of layers of DG, CA1 and CA3 of rat's hippocampus. Comparisons showed that the volumes of different layers in above-mentioned regions were significantly decreased following PB administration at 75 and 100 mg/kg doses. Conclusion: Long-term effect of PB on the volume of hippocampal regions is dose dependent. It is essential that the dose of PB be kept at a minimum effective dose to reduce its negative effects. It is also can be suggested that the CA1 volume reduction may be relevant to the reported impairment of learning and memory in PB treated patients. © 2009, Isfahan University of Medical Sciences(IUMS). All rights reserved.