title: Estradiol and ERβ agonists enhance recognition memory, and DPN, an ERβ agonist, alters brain monoamines.
abstract: Effects of estradiol benzoate (EB), ERα-selective agonist, propyl pyrazole triol (PPT) and ERβ-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 4h 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 2-4h 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 ERβ 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 ERβ 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.
authors.affiliation: Biopsychology and Behavioral Science Subprogram, Graduate Program in Psychology, Graduate Center of City University of New York, NY 10016, USA.
authors.forename: Luis F
authors.initials: LF
authors.lastname: Jacome
authors.forename: Claris
authors.initials: C
authors.lastname: Gautreaux
authors.forename: Tomoko
authors.initials: T
authors.lastname: Inagaki
authors.forename: Govini
authors.initials: G
authors.lastname: Mohan
authors.forename: Stephen
authors.initials: S
authors.lastname: Alves
authors.forename: Laura S
authors.initials: LS
authors.lastname: Lubbers
authors.forename: Victoria
authors.initials: V
authors.lastname: Luine
mesh_terms: D000818:Animals; D015306:Biogenic Monoamines / Q000378:metabolism; D001921:Brain / Q000187:drug effects / Q000378:metabolism*; D004193:Discrimination Learning / Q000187:drug effects; D004958:Estradiol / Q000008:administration & dosage / Q000502:physiology*; D047629:Estrogen Receptor beta / Q000819:agonists*; D004967:Estrogens / Q000494:pharmacology; D005106:Exploratory Behavior / Q000187:drug effects / Q000502:physiology; D005260:Female; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism; D018782:Maze Learning / Q000187:drug effects / Q000502:physiology; D008570:Memory, Short-Term / Q000187:drug effects* / Q000502:physiology; D017072:Neostriatum / Q000187:drug effects / Q000378:metabolism; D009570:Nitriles / Q000494:pharmacology; D010052:Ovariectomy; D010636:Phenols; D017397:Prefrontal Cortex / Q000187:drug effects / Q000378:metabolism; D011422:Propionates / Q000494:pharmacology; D011720:Pyrazoles / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D021641:Recognition, Psychology / Q000187:drug effects / Q000502:physiology*; D013037:Spatial Behavior / Q000187:drug effects / Q000502:physiology; D018709:Statistics, Nonparametric
chemical_list: C486182:2,3-bis(4-hydroxyphenyl)-propionitrile; D015306:Biogenic Monoamines; D047629:Estrogen Receptor beta; D004967:Estrogens; D009570:Nitriles; D010636:Phenols; D011422:Propionates; D011720:Pyrazoles; C486184:4,4',4''-(4-propyl-((1)H)-pyrazole-1,3,5-triyl) tris-phenol; D004958:Estradiol