Neuroscience Letters 364 (2004) 63–66 Scopolamine-induced amnesia can be prevented by heat shock pretreatment in rats Ching-Hsia Hung a , Mao-Tsun Lin b,∗ , Jyh-Fei Liao c , Jhi-Joung Wang b a Institute of Physiology, National Yang-Ming University Medical College, Taipei 112, Taiwan, ROC b Department of Medical Research, Chi-Mei Medical Center, Tainan 710, Taiwan, ROC c Institute of Pharmacology, National Yang-Ming University Medical College, Taipei 112, Taiwan, ROC Received 3 June 2003; received in revised form 5 January 2004; accepted 10 February 2004 Abstract The current study used the passive avoidance test to examine whether heat shock pretreatment has an effect on the memory impairment induced by scopolamine. Heat shock protein (HSP) 72 overexpression was detected in different brain structures in rats 16 h after heat shock treatment, but not in rats receiving no heat shock or 48 h after heat shock treatment. The step-through latency of either pre- or post-training administration of scopolamine in rats 16 h after heat shock treatment was significantly higher than those of the rats receiving no heat shock or 48 h after heat shock treatment. However, rats, 16 h after heat shock treatment and having been given scopolamine, performed no better than rats treated only with scopolamine. Hence, the present results indicate that heat shock has a protective, but not therapeutic, effect on the memory impairment induced by scopolamine by overexpression of HSP72 in rat brain. © 2004 Elsevier Ireland Ltd. All rights reserved. Keywords: Heat shock protein; Amnesia; Step-through passive avoidance; Scopolamine Heat shock protein (HSP) 72 is the major inducible HSP found in all living cells [20]. Following heat shock, ad- ministration of heavy metals or toxins, ischemia, and other stresses, the synthesis of HSP72 was increased [17]. Heat- ing an entire animal-induced HSP72 synthesis and protected the retina against light-induced damage [3] and the brain against ischemia [6,19]. Overproduction of HSP72 in trans- genic mice protected hippocampal neurons from focal is- chemia [13] and protected the myocardium from ischemia [14]. The involvement of brain HSP72 in learning was eval- uated by Western blot analysis in rats trained for an active avoidance task, and in passive and active controls [2]. Ex- pression of the HSP72 occurred in the cerebellum of rats trained for a two-way active avoidance task [1], whose mem- ory is preserved for months [10]. The current study used the passive avoidance test to examine whether HSP72 pre- conditioning by transient heat shock has a protective effect on the memory impairment induced by scopolamine in rats. Scopolamine can disrupt short-term memory in humans and animals [5,9,16]. ∗ Corresponding author. Tel.: +886-6-2812811; fax: +886-6-2517850. E-mail address: mtlin@ym.edu.tw (M.-T. Lin). Adult male Wistar rats (weight 285 ± 10 g) were obtained from the Animal Center of National Science Council and maintained on a 12-h light and 12-h dark cycle (light on be- tween 08:00 and 19:00 h) with food and tap water ad libitum. Each rat was put through the adaptation trial by placing it in the illuminated compartment, facing away from the dark compartment. After 10 s, the door between these two boxes was opened and the rat moved into the dark compartment freely. The latency to leave the illuminated compartment was recorded. Twenty-four hours after the adaptation trial, the rat received the training trial. The training trial is similar to the adaptation trial except that the door is closed automatically as soon as the rat steps into the dark compartment and an inescapable foot shock (current intensity 0.6 mA, frequency 5 Hz, and pulse duration 20 ms) is delivered through the grid floor for 5 s. The retention (or retesting) trial was performed 24 h after the training trial in the same manner without the electric shock and the latency of step-through to the dark compartment was recorded. The maximum cut-off time for step-through latency was 300 s. For heat shock treatment, rats under general anesthesia (40 mg kg -1 sodium pentobarbital, i.p.) were heated gently with an electric pad. The colonic temperature of the heated 0304-3940/$ – see front matter © 2004 Elsevier Ireland Ltd. All rights reserved. doi:10.1016/j.neulet.2004.02.074