Physiology & Behavior 69 (2000) 511–525 0031-9384/00/$ – see front matter © 2000 Elsevier Science Inc. All rights reserved. PII: S0031-9384(00)00206-7 Red ginseng ameliorated place navigation deficits in young rats with hippocampal lesions and aged rats Yong-Mei Zhong a , Hisao Nishijo a , Teruko Uwano a , Ryoi Tamura a , Kazuko Kawanishi b , Taketoshi Ono a, * a Department of Physiology, Faculty of Medicine, Toyama Medical and Pharmaceutical University, Sugitani 2630, Toyama 930-0194, Japan; b Department of Pharmacognosy, Kobe Pharmaceutical University, Kobe 658-8558, Japan Received 21 October 1999; received in revised form 7 December 1999; accepted 3 January 2000 Abstract Effects of hippocampal lesions and aging on spatial learning and memory and ameliorating effects of red ginseng on learning deficits were investigated in the following two experiments: performance of young rats with selective hippocampal lesions with red ginseng by mouth (p.o.; Experiment 1) and aged rats with red ginseng (p.o.; Experiment 2) in the spatial tasks was compared with that of sham-oper- ated or intact young rats. Each rat in these two behavioral experiments was tested with the three types of spatial-learning tasks (distance movement task, DMT; random-reward place search task, RRPST; and place-learning task, PLT) in a circular open field using intracranial self-stimulation as reward. The results in the DMT and RRPST tasks indicated that motivational and motor activity of young rats with hippocampal lesions with and without ginseng were not significantly different from that of sham-operated young rats in Experiment 1. However, young rats with hippocampal lesions displayed significant deficits in the PLT task. Treatment with red ginseng significantly ameliorated place-navigation deficits in young rats with hippocampal lesions on the PLT task. Similarly, red ginseng improved perfor- mance of aged rats on the PLT task in Experiment 2. The results, along with previous studies showing significant effects of red ginseng on the central nervous system, suggest that red ginseng ameliorates learning and memory deficits through effects on the central nervous sys- tem, partly through effects on the hippocampal formation. © 2000 Elsevier Science Inc. All rights reserved. Keywords: Place learning; Intracranial self-stimulation; CA1 subfield; Delayed neuronal death; Aged rats; Red ginseng 1. Introduction Neuropsychological studies in both monkeys and hu- mans suggested that hippocampal lesions induced deficits in memory formation [54,57,67]. The hippocampal formation is most susceptible to senescence-related pathological changes, such as those in senile dementia and especially in Alzheimer’s disease [10,11,23,35,43]. Studies of humans and experimental animals demonstrated that the hippocam- pal formation was also vulnerable to cerebral ischemia, which significantly impaired memory [43,61,62,65,67]. In particular, the CA1 cell layer of the hippocampal formation was strikingly vulnerable to ischemia, and in some cases, cell death in the CA1 subfield was associated with pure memory loss, almost without other neurological or neuro- pathological signs, in humans [12,24,67], suggesting that it may be sufficient to cause memory disturbance. This selec- tive vulnerability of the CA1 subfield has been confirmed in several animal models of global cerebral ischemia [42,46, 47,56]. Taken together, these studies strongly suggest that the hippocampal formation is one of the major regions re- sponsible for cognitive and memory disorders. Recently, we developed a protocol for the study of hip- pocampal neuron activity in rats that combines rewarding intracranial self-stimulation (ICSS) with video monitoring of the subject’s movement and location within the open field [17]. The ICSS reward was delivered in the cases of the following three navigation paradigms: when the rat (a) traveled a distance predetermined by an experimenter, (b) entered an experimenter-determined reward area (this place was randomly varied in sequential trials; random-reward search task, RRPST), or (c) entered two fixed, specific places (when it returned to one of those places after a visit to the other one; place learning task, PLT). The use of ICSS as a reward [55] offers the following advantages over food or water rewards: (a) rapid learning of a task, (b) lack of satiation, and (c) absence of visual and olfactory information regarding the reward. This protocol enables us to perform many trials under different conditions within a short time and in a well- * Corresponding author. Tel.: +81-76-434-7220; Fax: +81-76-434-5013. E-mail address: onotake@toyama-mpu.ac.jp