Physiology &Behavior, Vol. 53, pp. 1001-1002, 1993 0031-9384/93 $6.00 + .00 Printed in the USA. Copyright© 1993PergamonPressLtd, EGb 761 Inhibits Stress-Induced Polydipsia in Rats ELENA B. RODRIGUEZ DE TURCO,* MARIE THERESE DROY-LEFAIX t AND NICOLAS G. BAZAN .1 *Louisiana State University Medical Center School of Medicine, LSU Eye Center and Neuroscience Center, 2020 Gravier Street, Suite B, New Orleans, LA 70112, and -?IPSEN Laboratories, 30 Rue Cambronne, 75015 Paris, France Received 17 August 1992 RODRIGUEZ DE TURCO, E. B., M. T. DROY-LEFAIX AND N. G. BAZAN. EGb 761 inhibits stress-inducedpolydipsia in rats. PHYSIOL BEHAV 53(5) 1001-1002, 1993.--The effect of daily treatments with Ginkgo biloba extract (EGb 761, 1PSEN, France) on body weight and water intake of rats was followed for 15 days. During this period, two groups of rats, under slight ether anesthesia, were intubated and fed either EGb 761 ( 100 mg/kg b.wt. in 5% ethanol) or, for sham controls, 5% ethanol alone (6.6 ml/kg b.wt.). The increase in body weight was similar for the control and experimental groups. However, during the same period of time, the water intake, ml water/g b.wt./24 h, increased 37% in the controls. In EGb 761-treated rats, water intake remained unchanged. This suggests that EGb 761 treatment inhibits the development of polydipsia due to the stress of daily handling and intubation. EGb 761 Polydipsia Water intake Rats Stress THE natural extract of Ginkgo biloba leaves, EGb 761 (Tanakan, IPSEN International Ltd., London), is a complex mixture of pharmacologically active substances with a broad spectrum of therapeutic effects (5). One group of active substances present in EGb 761 is terpenoids, which are known for their platelet- activating factor (PAF) antagonistic properties (4). Ginkgolides, in combination with flavonoids, also present in EGb 761 and known for their free scavenger properties, may contribute to the overall beneficial effects of EGb 761 (5). Stimulation of cerebral circulation, leading to better tissue oxygenation, combined with the protection of membrane lipidic structure from free radical- triggered damage, may contribute to alleviating deficiencies in the central nervous system linked to aging and/or triggered by traumatic insults (i.e., ischemia) ( 1 ). In fact, EGb 761 given orally modulates seizure-induced phospholipase C activation in the hippocampus (2). This effect may elicit neuroprotection by de- creasing inositol lipid degradation and the generation of second messengers that enhance intracellular calcium ionization and other disturbances of neural signal transduction (2). In the course of our present ongoing studies about the in vivo effect of EGb 761 on lipid-derived second messengers in the central nervous system, we followed up possible effects of the drug in body weight and water intake during the chronic treatment of rats. The pres- ent observation suggests a central effect of EGb 761 preventing the development of stress-induced polydipsia. METHOD Male Wistar rats (250-290 g b.wt.), obtained from Charles River Laboratories, were maintained under a 12-h light and dark cycle and given food and water on demand. Animals, housed four in a cage, were divided into two groups. Experimental an- imals were treated each morning for 14 days with Ginkgo biloba extract (EGb 76 l) dissolved in ethanol (5%). The drug was ad- ministered PO (100 mg/kg b.wt.) under light ether anesthesia. Sham control animals were handled in the same manner as ex- perimental ones except they received the vehicle alone (ethanol 5%, 6.6 ml/kg b.wt.). Animals were weighed daily and the volume of water drunk over 24-h periods was measured. RESULTS AND DISCUSSION Body Weight and Water Intake During the 15 days of treatment, the body weight both in controls and in EGb 761-treated rats increased by 29% (from 271 + 15 to 350 _+ 19 g) and 28% (from 271 + 16 to 346 _+ 18 g), respectively (Fig. 1). Water intake (ml water/rat/24 h) in sham animals increased by 78% (from 32.3 --_ 4.1 to 57.4 _+ 4.2 ml), while in EGb 761-treated rats, water intake increased by only 39% (from 32.2 + 5.1 to 44.7 _+ 2.1 ml). Since an increase in water intake will occur in parallel with an increase in body weight, values were normalized to ml water/kg of b.wt./24 h (Fig. 2). In Requests for reprints should be addressed to Nicolas G. Bazan, M.D., Ph.D., LSU Eye Center and Neuroscience Center, 2020 Gravier Street, Suite B, New Orleans, LA 70112. 1001