Intra-perirhinal cortex administration of estradiol, but not an ER[beta] agonist, modulates object-recognition memory in ovariectomized rats

* Intra-PRh E2 enhances novelty preference following delays of 0.5min to 72h. * Intra-PRh E2 reduces accuracy on the DNMS task following a 5-min delay. * Intra-PRh DPN enhances novelty preference following delays of 0.5min to 72h. * Intra-PRh DPN does not influence accuracy on the DNMS task. Intra-rhinal cortical infusion of 17-[beta] estradiol (E2, 244.8pg/μl) enhances performance on the Novel-Object Preference (NOP) test and impairs accuracy on the delayed nonmatching-to-sample (DNMS) task in the same set of ovariectomized rats (Gervais, Jacob, Brake, & Mumby, 2013). These results appear paradoxical, as normal performance on both tests require intact object-recognition memory (ORM) ability. While demonstrating a preference for the novel object requires recognizing the sample object, rodents can recognize the sample object and still fail to demonstrate a preference. Therefore, enhanced NOP test performance is consistent with both improved ORM and increased novel-object exploration independent of memory processes. There is some evidence suggesting that estrogen receptor (ER) [beta] agonists enhance NOP test performance (Jacome et al., 2010), but no study to date has examined the role of this receptor in DNMS task performance in rodents. The aim of the present study was to determine whether intra-PRh infusion of an ER [beta] agonist, diarylpropionitrile (DPN, 2μg/μl), has divergent effects on novel-object preference (i.e. novelty preference) and accuracy on the DNMS task. Ovariectomized (OVX) rats (n =7) received chronic low E2 (∼22pg/ml serum) replacement, then intra-PRh infusion of DPN (2μg/μl), E2 (244.8pg/μl), or vehicle before each mixed-delay session (0.5-5min) of the DNMS task. A different set of OVX rats (n =10) received the same infusions before each NOP test trial, and were tested either 4 or 72h later. Consistent with Gervais et al. (2013), intra-PRh E2 reduced accuracy on the DNMS task following a 5-min retention delay and enhanced novelty preference on both tests. Intra-PRh DPN was associated with accuracy that was similar to the vehicle-infusion condition, despite enhancing novelty preference on both tests. The accuracy results suggest that while intra-PRh E2 impairs ORM, ER[beta] does not play a role. However, ER[beta] in the PRh appears to be important for the expression of novelty preference, in a manner that is unaffected by retention delay. These findings suggest that the modulation of novelty preference by intra-PRh E2/ER[beta] may be du