Neurobiology of Aging, Vol. 2, pp. 209-213, 1981. Printed in the U.S.A. Behavioral Effects of Phosphatidylserine in Aged Rats F. DRAGO, P. L. CANONICO AND U. SCAPAGNINI Department of Pharmacology, University of Catania Medical School 95125 Catania, Italy Received 29 September 1980 DRAGO F., P. L. CANONICO AND U. SCAPAGNIN1. Behavioral effects of phosphatidylserine in aged rats. NEUROBIOL. AGING 2(3)209-213, 1981.--The behavioral effects of 5 days of administration of phosphatidylserine (PS) was studied in aged rats. The intraperitoneal (5, 10, and 20 mg/kg) or intracerebroventricular (5, 10, and 20/~g/2 V.I)injection ofPS liposomes caused a facilitated acquisition of active avoidance behavior as studied in shuttle-box and pole jumping test situations. The retention of active and passive avoidance responses was also improved. No substantial difference between PS-treated and control animals was apparent either in the responsiveness to electrical footshock or in the motor activity tested in an open field. Grooming behavior appeared to be enhanced in rats treated with the highest dose of the substance. Since PS affects both central catecholaminergic and cholinergic transmission, which is known to be impaired in old animals, the possibility that the behavioral effects of PS involve brain dopamine and/or acetylcholine systems is discussed. Phosphatidylserine Active avoidance Passive avoidance Open field Age-related behavioral deficits Responsiveness to electrical footshock THE more rapid forgetting in old rats is generally interpreted as resulting from a memory storage impairment [15]. In par- ticular, some of these behavioral changes may be the result of age-related alterations in central neurotransmission sys- tems. Central catecholamine systems are impaired in old animals [8, 13, 19, 23]. Also, changes in cholinergic systems occur naturally in aged animals and humans [3, 18, 26, 30]. Evidence has been obtained that central catecholamine sys- tems, particularly the dopaminergic systems, play a funda- mental role in learning and memory processes [4, 6, 25, 27]. Thus, it has been postulated that learning and memory defi- cits in the elderly may be related to an impairment of central catecholaminergic systems [15], Loss of cholinergic trans- mission in the brain may also contribute to the motor and mental impairments that often accompany old age [ 18,26]. The acidic phospholipid phosphatidylserine (PS) may in- fluence the release ofcatecholamines [28] and acetylcholine [20] in the brain. Present experiments were aimed at investigating whether the administration of PS to old rats would influence their learning and memory processes. In order to avoid the prob- lem of the blood-brain barrier, we administered the sonicated suspension of PS either peripherally or via a cannula perma- nently implanted into the cerebroventricular system. METHOD Animals Male rats of an inbred Wistar strain, weighing 750__30 g, 22 months old (+__7days), were used throughout the experi- ments. Animals were housed two/three to a cage with food and water supplied ad lib, under a constant light-dark cycle (lights on between 5.00 and 20.00). Seven days prior the experimental session a number of animals were implanted with permanent plastic cannulae into their third ventricle (foramen interventriculare, Konig and Klippel, A6360). Only those animals which showed good physical conditions and normal spontaneous behavior were used. All animals were used only once in the behavioral experiments. Drugs Purified PS from bovine brain was obtained from FIDIA Laboratories (Abano Terme, Italy). The substance was dis- solved in chloroform and methanol. Aliquots were dried under reduced pressure at 4°C. The dried residue, kept in a nitrogen atmosphere, was re-suspended in 0.05 M Tris buffer (pH 7.4). The suspension was sonicated under a nitrogen stream at 0°C for 8 min with a Blackstone sonicator. This suspension of PS liposomes was injected intraperitoneaUy to rats in a daily dose of 5, 10 or 20 mg/kg for 5 days. The suspension was also injected intracerebroventricularly to animals with permanent cannula in a daily dose of 5, 10 or 20 ~.g/2 /~l for 5 days. Control animals received IP or ICV injection of 0.05 M Tris buffer (pH 7.4). The behavioral tests started 30 rain after the last treatment. Behavioral Tests Active avoidance behavior was studied in a shuttle-box and a pole jumping situation. The shuttle-box acquisition was studied in a single session test that has been described elsewhere [2]. Briefly, the rats were trained to avoid the unconditioned stimulus (US) of a scrambled electrical foot- shock (0.20 mA) delivered through the grid floor. The con- ditioned stimulus (CS) was a buzzer presented for 3 sec prior Copyright e 1981 ANKHO International Inc.--0197-4580/81/030209-05501.00/0