Estrogens and progestins enhance spatial learning of intact and ovariectomized rats in the object placement task

Abstract

Steroid modulation of cognitive function has focused on estrogen (E(2)), but progestins naturally co-vary with E(2) and may also influence cognitive performance. Spatial performance in the object placement task over endogenous hormonal states in which E(2) and progestins vary, and when E(2) and/or progestins were administered, was examined. Experiment 1: Rats in proestrus or estrus had significantly better performance in the object placement task than did diestrus rats. Experiment 2: Rats in the third trimester, post-partum, or lactation exhibited significantly better performance in the object placement task than did rats in the first trimester. Experiment 3: Ovariectomized (ovx) rats administered 17beta-estradiol (0.9 mg/kg), subcutaneously (sc), progesterone (P; 4 mg/kg, sc), or E(2) and P, immediately after training in the object placement task, performed significantly better when tested 4h later, than did control rats administered vehicle (sesame oil 0.2 cc). Experiment 4: ovx rats administered E(2) or P with a 1.5h delay after training in the object placement task, did not perform differently than vehicle-administered controls. Experiment 5: ovx rats administered post-training E(2), which has a high affinity for both E(2) receptor (ER)alpha and beta isoforms, or propyl pyrazole triol (PPT; 0.9 mg/kg, sc), which is more selective for ERalpha than ERbeta, had significantly better performance in the object placement task than did rats administered vehicle or diarylpropionitrile (DPN; 0.9 mg/kg, sc), an ERbeta selective ligand. Experiment 6: ovx rats administered P, or its metabolite, 5alpha-pregnan-3alpha-ol-20-one (3alpha,5alpha-THP; 4 mg/kg, sc), immediately post-training performed significantly better in the object placement task than did vehicle control rats. Thus, performance in the object placement task is better when E(2) and/or P are naturally elevated or when E(2), the ERalpha selective ER modulator PPT, P, or its metabolite, 3alpha,5alpha-THP, are administered post-training.

Figure 1

Mean percent of time (± standard error) proestrous (n=25; stripped bar) and estrous (n=25; filled bar) rats spent exploring the displaced object as compared to diestrous controls (n=25; open bar). * Indicates significant difference from diestrus (p ≤ 0.05).

Figure 2

Mean percent of time (± standard error) 3^rd trimester (n=25; stripped bar), post-partum (n=23; filled bar), and lactating (n=22; shaded bar) rats spent exploring the displaced object as compared to 1^st trimester controls (n=25). * Indicates significant difference from 1^st trimester (p ≤ 0.05).

Figure 3

Mean percent (± standard error) of time spent exploring the displaced object of ovx rats administered E₂ (n=18; stripped bar), P (n=21; filled bar) or E₂ + P (n=18; shaded bar) immediately after training compared to vehicle (n=21) * Indicates significant difference from ovx vehicle (p ≤ 0.05).

Figure 4

Mean percent (± standard error) of time spent exploring the displaced object of ovx rats administered E₂ (n=16; stripped bar), P (n=16; filled bar) or E₂ + P (n=16; shaded bar) 1.5 hours after training compared to vehicle (n=16).

Figure 5

Mean percent (± standard error) of time ovx rats administered post-training E₂ (n=17; stripped bar), PPT (n=17; filled bar), or DPN (n=17; shaded bar) rats spent exploring the displaced object as compared to ovx vehicle controls (n=17). * Indicates significant difference from ovx (p ≤ 0.05).

Figure 6

Mean percent (± standard error) of time ovx rats administered post-training P (n=19; stripped bar) or 3α-5α-THP (n=18; filled bar) spent exploring the displace object as compared to ovx vehicle controls (n=21). * Indicates significant difference from ovx vehicle (p ≤ 0.05).