Estradiol and ERβ agonists enhance recognition memory, and DPN, an ERβ agonist, alters brain monoamines

Effects of estradiol benzoate (EB) ER alpha-selective agonist propyl pyrazole triol (PPT) and ER beta-selective agonists diarylpropionitrile (DPN) and Compound 19 (C-19) on memory were investigated in OVX rats using object recognition (OR) and placement (OP) memory tasks Treatments were acute (behavior 4 h later) or sub chronic (daily injections for 2 days with behavior 48 h later) Objects were explored in sample trials (T1) and discrimination between sample (old) and new object/location in recognition trials (T2) was examined after 2-4 h inter-trial delays Subjects treated sub chronically with EB DPN and C-19 but not PPT discriminated between old and new objects and objects in old and new locations suggesting that at these doses and duration of treatments estrogenic interactions with ER beta contribute to enhancements in recognition memory Acute injections of DPN but not PPT immediately after T1 also enhanced discrimination for both tasks (C19 was not investigated) Effects of EB DPN and PPT on anxiety and locomotion measured on elevated plus maze and open field did not appear to account for the mnemonic enhancements Monoamines and metabolites were measured following DPN treatment in subjects that did not receive behavioral testing DPN was associated with alterations in monoamines in several brain areas indexed by the metabolite 3-methoxy-4-hydroxyphenylglycol (MHPG) or the MHPG/norepinephrine (NE) ratio NE activity was increased by 60-130% in the prefrontal cortex (PFC) and ventral hippocampus and NE activity was decreased by 40-80% in the v diagonal bands and CA1 Levels of the dopamine (DA) metabolite homovanillic acid (HVA) Increased 100% in the PFC and decreased by 50% in the dentate gyrus following DPN treatment The metabolite of serotonin 5-hydroxyindole acetic acid (5-HIAA) was Increased in the PFC and CA3 by approximately 20% No monoaminergic changes were noted in striatum or medial septum Results suggest that ER beta mediates sub chronic and acute effects of estrogens on recognition memory and that memory enhancements by DPN may occur in part through alterations in monoaminergic containing systems primarily in PFC and hippocampus (C) 2010 Elsevier Inc All rights reserved