PMID- 19223011 OWN - NLM STAT- MEDLINE DCOM- 20090817 LR - 20211020 IS - 1873-7544 (Electronic) IS - 0306-4522 (Print) IS - 0306-4522 (Linking) VI - 160 IP - 1 DP - 2009 Apr 21 TI - Dose-dependent effects of post-training estradiol plus progesterone treatment on object memory consolidation and hippocampal extracellular signal-regulated kinase activation in young ovariectomized mice. PG - 6-12 LID - 10.1016/j.neuroscience.2009.02.024 [doi] AB - Previous work from our laboratory has shown that the ability of estradiol to enhance object memory consolidation in young ovariectomized mice is dependent on dorsal hippocampal activation of the extracellular signal-regulated kinase/mitogen-activated protein kinase (ERK/MAPK) signaling pathway [Fernandez SM, Lewis MC, Pechenino AS, Harburger LL, Orr PT, Gresack JE, Schafe GE, Frick KM (2008) Estradiol-induced enhancement of object memory consolidation involves hippocampal extracellular signal-regulated kinase activation and membrane-bound estrogen receptors. J Neurosci 28:8660-8667]. However, it is unclear if estradiol modulates memory or ERK activation similarly in the presence of progesterone. Therefore, the present study investigated effects of combined estradiol and progesterone treatment on object memory consolidation and dorsal hippocampal ERK activation in young ovariectomized C57BL/6 mice. Object memory was tested in a novel object recognition task. Immediately after training, mice received intraperiotoneal (i.p.) injections of vehicle, 17beta-estradiol (E(2); 0.2 mg/kg), or E(2) plus 5, 10, or 20 mg/kg progesterone (P). Forty-eight hours later, mice receiving E(2) alone or E(2) plus 10 or 20 mg/kg P exhibited significantly enhanced memory for the novel object relative to chance, whereas those receiving vehicle or E(2) plus 5 mg/kg P spent no more time than chance with the novel object. Two weeks later, ERK phosphorylation was measured in the dorsal hippocampus 1 h after i.p. injection of vehicle, E(2), or E(2) plus P. Consistent with our previous work [Fernandez SM, Lewis MC, Pechenino AS, Harburger LL, Orr PT, Gresack JE, Schafe GE, Frick KM (2008) Estradiol-induced enhancement of object memory consolidation involves hippocampal extracellular signal-regulated kinase activation and membrane-bound estrogen receptors. J Neurosci 28:8660-8667], E(2) alone significantly increased phospho-p42 ERK protein levels in the dorsal hippocampus relative to vehicle controls. In contrast, no combination of E(2) and P affected dorsal hippocampal phospho-ERK levels. These data indicate that, unlike E(2) alone, the beneficial effects of combined E(2) plus P treatment on memory are not associated with ERK activation in the dorsal hippocampus 1 h after treatment, and suggest that E(2) alone and combined E(2) plus P may influence ERK activation in different time frames or enhance memory through different mechanisms. FAU - Harburger, L L AU - Harburger LL AD - Department of Psychology, Stern College for Women, Yeshiva University, New York, NY 10016, USA. FAU - Saadi, A AU - Saadi A FAU - Frick, K M AU - Frick KM LA - eng GR - R01 AG022525-02/AG/NIA NIH HHS/United States GR - R01 AG022525-03/AG/NIA NIH HHS/United States GR - R01 AG022525/AG/NIA NIH HHS/United States GR - R01 AG022525-04/AG/NIA NIH HHS/United States GR - R01 AG022525-01A2/AG/NIA NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't DEP - 20090214 PL - United States TA - Neuroscience JT - Neuroscience JID - 7605074 RN - 0 (Estrogens) RN - 0 (Progestins) RN - 4G7DS2Q64Y (Progesterone) RN - 4TI98Z838E (Estradiol) RN - EC 2.7.11.24 (Extracellular Signal-Regulated MAP Kinases) RN - EC 2.7.11.24 (Mitogen-Activated Protein Kinase 1) RN - EC 2.7.11.24 (Mitogen-Activated Protein Kinase 3) SB - IM MH - Animals MH - Blotting, Western MH - Dose-Response Relationship, Drug MH - Enzyme Activation/drug effects MH - Estradiol/*administration & dosage MH - Estrogens/*administration & dosage MH - Extracellular Signal-Regulated MAP Kinases/*metabolism MH - Female MH - Hippocampus/drug effects/enzymology MH - Mice MH - Mice, Inbred C57BL MH - Mitogen-Activated Protein Kinase 1/metabolism MH - Mitogen-Activated Protein Kinase 3/metabolism MH - Ovariectomy MH - Phosphorylation/drug effects MH - Progesterone/*administration & dosage MH - Progestins/*administration & dosage MH - Recognition, Psychology/*drug effects PMC - PMC2668744 MID - NIHMS95881 EDAT- 2009/02/19 09:00 MHDA- 2009/08/18 09:00 PMCR- 2010/04/21 CRDT- 2009/02/19 09:00 PHST- 2008/11/05 00:00 [received] PHST- 2009/02/11 00:00 [revised] PHST- 2009/02/12 00:00 [accepted] PHST- 2009/02/19 09:00 [entrez] PHST- 2009/02/19 09:00 [pubmed] PHST- 2009/08/18 09:00 [medline] PHST- 2010/04/21 00:00 [pmc-release] AID - S0306-4522(09)00231-0 [pii] AID - 10.1016/j.neuroscience.2009.02.024 [doi] PST - ppublish SO - Neuroscience. 2009 Apr 21;160(1):6-12. doi: 10.1016/j.neuroscience.2009.02.024. Epub 2009 Feb 14.