Elsevier

Hormones and Behavior

Volume 41, Issue 1, February 2002, Pages 22-32
Hormones and Behavior

Regular Article
Effects of Ovariectomy and Estrogen Treatment on Learning and Hippocampal Neurotransmitters in Mice

https://doi.org/10.1006/hbeh.2001.1738Get rights and content

Abstract

This study examined the effects of long-term estrogen treatment (sc 17β-estradiol minipellets) on learning in C57BL/6J female and male mice using a position discrimination task in the T-maze and a win-stay task (1/8 arms baited) in the radial arm maze (RAM). In addition, hippocampal monoamines and ChAT activity were measured at the end of the study and correlated to task performance. Female sham-operated (gonadally intact) and ovariectomized (OVX) mice were treated with estrogen either for 7 or 40 days before the behavioral tests and intact male mice for 7 days before the behavioral tests. In sham-operated mice the 40-day estrogen treatment improved RAM performance and in OVX mice both the 7- and 40-day estrogen treatments improved the performance in both maze tasks. The estrogen treatment also improved RAM performance in males. The hippocampal ChAT, NA, 5-HIAA, and DOPAC levels were decreased in OVX mice. Furthermore, the effects of estrogen treatment on the levels of hippocampal 5-HT and its metabolite 5-HIAA were different in sham-operated than in OVX mice. We could find no correlation between cognitive measures and neurochemical variables. This study gives new information about the effects of estrogen on learning and hippocampal neurotransmitters in mice.

References (51)

  • R.B. Gibbs

    Effects of gonadal hormone replacement on measures of basal forebrain cholinergic function

    Neuroscience

    (2000)
  • P. Jäkälä et al.

    The effects of p-chlorophenylalanine-induced serotonin synthesis inhibition and muscarinic blockade on the performance of rats in a 5-choice serial reaction time task

    Behav. Brain Res.

    (1992)
  • V. Luine et al.

    Spatial memory deficits in aged rats: Contributions of monoaminergic systems

    Brain Res.

    (1990)
  • V. Luine et al.

    Effects of estradiol on radial arm maze performance of young and aged rats

    Behav. Neural Biol.

    (1994)
  • V.N. Luine

    Estradiol increases choline acetyltransferase activity in specific basal forebrain nuclei and projection areas of female rats

    Exp. Neurol.

    (1985)
  • V.N. Luine et al.

    Estradiol enhances learning and memory in a spatial memory task and effects levels of monoaminergic neurotransmitters

    Horm. Behav.

    (1998)
  • M.M. Miller et al.

    Estrogen modulates spontaneous alternation and the cholinergic phenotype in the basal forebrain

    Neuroscience

    (1999)
  • M.G. Oliveira et al.

    Strategies used by hippocampal- and caudate-putamen-lesioned rats in a learning task

    Neurobiol. Learn. Mem.

    (1997)
  • M. Pisa et al.

    On the role of the dorsal noradrenergic bundle in learning and habituation to novelty

    Pharmacol. Biochem. Behav.

    (1988)
  • P. Polo-Kantola et al.

    The effect of short-term estrogen replacement therapy on cognition: A randomized, double-blind, cross-over trial in postmenopausal women

    Obstet. Gynecol.

    (1998)
  • M. Singh et al.

    Ovarian steroid deprivation results in a reversible learning impairment and compromised cholinergic function in female Sprague–Dawley rats

    Brain Res.

    (1994)
  • K. Taghzouti et al.

    Alternation behavior, spatial discrimination, and reversal disturbances following 6-hydroxydopamine lesions in the nucleus accumbens of the rat

    Behav. Neural Biol.

    (1985)
  • H. Tanila et al.

    Effect of sex and age on brain monoamines and spatial learning in rats

    Neurobiol. Aging

    (1994)
  • I.A. Wilson et al.

    Estrogen and NMDA receptor antagonism: Effects upon reference and working memory

    Eur. J. Pharmacol.

    (1999)
  • J. Zhang et al.

    Neurochemical characteristics and behavioral responses to psychological stress in ovariectomized rats

    Pharmacol. Res.

    (1999)
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      Similarly, Marrocco et al., 2017 found that ovariectomy attenuated stress-induced impairments in behavior but that exogenous treatment with estradiol did not restore the effect and depended on genotype (heterozygous BDNF Val66Met carriers), suggesting a more complex interplay beyond circulating estradiol alone. Interestingly, evidence indicates that ovariectomy induces more male-typic performance on learning and memory tasks (Gibbs and Johnson, 2008; Heikkinen et al., 2002) suggesting a complex role for the endocrine system in cognitive function. Future work is needed to determine the extent to which chronic stress at vulnerable developmental timepoints, particularly for endocrine refinement, may shift the balance between sex-steroid receptors and circulating hormones and subsequent implications for neural function.

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