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

Neurobiol Learn Mem. 2006 Mar;85(2):183-91. doi: 10.1016/j.nlm.2005.10.003. Epub 2005 Dec 1.


Estradiol (17beta-E2) can have mnemonic-enhancing effects; however, its mechanisms for these effects are not well-understood. The present studies examined effects of 17beta-E2 and selective estrogen receptor modulators (SERMs) on emotional and spatial memory of female, Long-Evans rats. First, whether or not 17beta-E2 has dose-dependent effects on inhibitory avoidance memory was investigated. Only the highest concentration of 17beta-E2 examined (10 microg), which produces physiological concentrations of E2, 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 17beta-E2. Compounds utilized were, the ERalpha-selective SERMs, propyl pyrazole triol (PPT) or 17alpha-E2, the ERbeta-specific SERMs, diarylpropionitrile (DPN) or 7,12-dihydrocoumestan (coumestrol), or vehicle (oil). Post-training administration of 10 microg 17beta-E2 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 17beta-E2, coumestrol, or DPN, compared to vehicle (Experiment 3). Co-administration of 17alpha-E2&DPN enhanced inhibitory avoidance memory similar to that seen following 17beta-E2 or coumestrol (Experiment 4). Administration of E2 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 17beta-E2, 17alpha-E2, or PPT, compared to vehicle (Experiment 6). These data suggest that: E2's actions at ERbeta, rather than ERalpha, may enhance spatial memory, E2's actions at ERalpha can facilitate sexual behavior, and that E2's actions involving both ERalpha and ERbeta may be important for emotional memory.

Publication types

  • Comparative Study
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Arousal / drug effects
  • Avoidance Learning / drug effects*
  • Brain / drug effects
  • Coumestrol / pharmacology
  • Dose-Response Relationship, Drug
  • Emotions / drug effects*
  • Escape Reaction / drug effects*
  • Estradiol / pharmacology*
  • Estrogen Receptor Modulators / pharmacology*
  • Estrogen Receptor alpha / drug effects
  • Fear / drug effects*
  • Female
  • Inhibition, Psychological*
  • Maze Learning / drug effects*
  • Mental Recall / drug effects*
  • Nitriles / pharmacology
  • Orientation / drug effects*
  • Phenols
  • Propionates / pharmacology
  • Pyrazoles / pharmacology
  • Rats
  • Rats, Long-Evans
  • Reaction Time / drug effects
  • Receptors, Estrogen / drug effects*
  • Sexual Behavior, Animal / drug effects


  • Estrogen Receptor Modulators
  • Estrogen Receptor alpha
  • Nitriles
  • Phenols
  • Propionates
  • Pyrazoles
  • Receptors, Estrogen
  • diarylpropionitrile
  • estrogen receptor-related receptor beta
  • 4,4',4''-(4-propyl-((1)H)-pyrazole-1,3,5-triyl) tris-phenol
  • Estradiol
  • Coumestrol