ERβ-selective SERMs produce mnemonic-enhancing effects in the inhibitory avoidance and water maze tasks

Abstract

Estradiol (17β-E 2) can have mnemonic-enhancing effects; however, its mechanisms for these effects are not well-understood. The present studies examined effects of 17β-E 2 and selective estrogen receptor modulators (SERMs) on emotional and spatial memory of female, Long-Evans rats. First, whether or not 17β-E 2 has dose-dependent effects on inhibitory avoidance memory was investigated. Only the highest concentration of 17β-E 2 examined (10 μg), which produces physiological concentrations of E 2, was effective at enhancing inhibitory avoidance memory (Experiment 1). Further studies were designed to elucidate whether SERMs may produce mnemonic effects similar to those of 17β-E 2. Compounds utilized were, the ERα-selective SERMs, propyl pyrazole triol (PPT) or 17α-E 2, the ERβ-specific SERMs, diarylpropionitrile (DPN) or 7,12-dihydrocoumestan (coumestrol), or vehicle (oil). Post-training administration of 10 μg 17β-E 2 or coumestrol enhanced memory in the inhibitory avoidance task compared to vehicle (Experiment 2). Memory in the water maze was enhanced by post-training administration of 17β-E 2, coumestrol, or DPN, compared to vehicle (Experiment 3). Co-administration of 17α-E 2&DPN enhanced inhibitory avoidance memory similar to that seen following 17β-E 2 or coumestrol (Experiment 4). Administration of E 2 2 h post-training was not effective at enhancing memory in the inhibitory avoidance or water maze tasks (Experiment 5). Lordosis of rats was enhanced by 17β-E 2, 17α-E 2, or PPT, compared to vehicle (Experiment 6). These data suggest that: E 2’s actions at ERβ, rather than ERα, may enhance spatial memory, E 2’s actions at ERα can facilitate sexual behavior, and that E 2’s actions involving both ERα and ERβ may be important for emotional memory.