In the next phase of the research, we administered DHEAS chronically to rats in their drinking water and then tested their spatial learning and memory in the Morris water maze. In this task, rats learn to escape from water immersion by learning and then remembering the location of a fixed platform, which is hidden just beneath the surface of the water (Brandeis et al., 1989
). Rats learn spatial information rapidly and are highly motivated to escape from the water. Thus, a reduction in the time to escape across training trials indicates that a rat has the motivation to escape the water and has learned the location of the hidden platform.
Rats were given the vehicle (lemonade-flavored water) or one of two doses of DHEAS mixed in the their drinking water (100 or 400 μg/100 ml) for 1 week prior to water maze training. The rats were given five training trials on day 1 in which they had up to 2 min/trial to learn the location of the hidden platform. On the second day of training all rats were given a single memory test trial. Rats that remembered the platform location took less time to find the platform than rats that had impaired memory of the platform location.
On the first day of training, all three groups reduced their time to find the hidden platform equally over the course of the five training trials, indicating that they had equivalent learning abilities and that they were all motivated to escape from the water. A difference in performance was observed on the 24-h memory test trial. As can be seen from the right-hand side of , rats given 100 μ
g/100 ml of DHEAS-treated water, but not those given 400 μ
g/100 ml, were superior (that is, had lower escape latencies) to rats treated with the vehicle or 400 μ
g/100 ml of DHEAS. Thus, the intermediate dose of DHEAS produced superior spatial memory performance compared to the other two groups (Diamond and Fleshner, 1999
FIGURE 1 A lower, but not a higher, dose of DHEAS enhanced spatial memory and hippocampal PB potentiation. Rats administered 100 μg/100 ml of DHEAS in their drinking water exhibited superior spatial memory (i.e., less time to swim to the hidden platform) (more ...)
What might be the basis of the DHEAS-induced enhancement of memory? To address this question, we recorded PB potentiation in the same animals that had been trained in the water maze. Once water maze training had been completed, the rats continued to receive DHEAS in their drinking water until the day in which the electrophysiological recordings took place. On that day, the rats were anesthetized with urethane (1.5 g/kg, ip) and PB was recorded in the CA1 region of the hippocampus according to methods described previously (Bennett et al., 1991
; Diamond et al., 1992
). The left-hand side of shows the magnitude of PB in the vehicle- and DHEAS-treated groups. The dose of DHEAS that enhanced spatial memory (l00 μ
g/100 ml) also increased the magnitude of PB potentiation. The magnitude of PB potentiation was relatively small in the control and high-dose groups (21 and 18% increases, respectively) and significantly greater in the group that received the intermediate dose (Diamond and Fleshner, 1999
). Thus, the enhanced memory observed in the rats that received the 100 μ
g/100 ml dose may have resulted from the enhanced expression of hippocampal synaptic plasticity (PB potentiation) occurring selectively at this dose.