title: 17β-estradiol replacement in ovariectomized female rats slows set 1 dorsolateral striatial-dependent learning and enhances learning of set 2 in an extradimensional set-shifting paradigm.
abstract: The role of estrogen in extradimensional set-shifting was evaluated with replacement of 17β-estradiol (E2) in ovariectomized (OVX) female rats. Rats were reinforced with food when they entered an arm of a plus-maze that was distinguished by visual and/or tactile cues (Set 1). In Set 2, reinforcement was shifted to construct a new association between food and visual/tactile cues that were different from Set 1. The purpose of using this extradimensional set-shifting task was to differentiate the effect of acute or continuous E2 on the dorsolateral (DLS) versus dorsomedial (DMS) striatum and medial prefrontal cortex (mPFC), because Set 1 and 2 learning, respectively, are associated with these particular brain regions. Results showed that compared to controls, acute E2-replaced female rats required more training trials to reach criterion in Set 1. Moreover, E2-replaced females showed a significant delay in the rate of acquisition of Set 1 learning compared to controls. In Set 2 there were no group differences in perseverative errors, which are reduced by mPFC activation, or when learning took place in a previously reinforced arm, a DMS-mediated effect. Despite this, control females required more training trials to learn Set 2 compared to Set 1, suggesting that prior learning in Set 1 interfered with Set 2 performance in non-E-replaced rats. In contrast, E2 groups learned Set 2 in fewer training trials than Set 1. These data suggest that E2 facilitates set shifting, apart from any apparent enhancement of DMS or mPFC function, perhaps by interfering with DLS-mediated Set 1 learning.
authors.affiliation: Department of Psychology, Christopher Newport University.
authors.forename: Olga
authors.initials: O
authors.lastname: Lipatova
authors.affiliation: Department of Psychological Science, University of Vermont.
authors.forename: Nicholas
authors.initials: N
authors.lastname: Wiener
authors.affiliation: Department of Psychological Science, University of Vermont.
authors.forename: Kelly
authors.initials: K
authors.lastname: Andrews
authors.affiliation: Department of Psychology, Saint Michael's College.
authors.forename: Ari P
authors.initials: AP
authors.lastname: Kirshenbaum
authors.affiliation: Department of Psychological Science, University of Vermont.
authors.forename: John T
authors.initials: JT
authors.lastname: Green
authors.affiliation: Department of Psychological Science, University of Vermont.
authors.forename: Donna J
authors.initials: DJ
authors.lastname: Toufexis
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D001288:Attention / Q000187:drug effects*; D003342:Corpus Striatum / Q000187:drug effects*; D003463:Cues; D004958:Estradiol / Q000494:pharmacology*; D004967:Estrogens / Q000494:pharmacology*; D005260:Female; D018782:Maze Learning / Q000187:drug effects; D010052:Ovariectomy; D051381:Rats; D017207:Rats, Sprague-Dawley; D012193:Reversal Learning / Q000187:drug effects; D012718:Set, Psychology
chemical_list: D004967:Estrogens; D004958:Estradiol