The organizational effects of gonadal steroids on sexually dimorphic spatial ability

Williams, Christina L.; Meck, Warren H.

doi:10.1016/0306-4530(91)90076-6

Cited by 408 publications

(224 citation statements)

References 58 publications

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“…All three tasks are disrupted by lesions of the hippocampus or NDMA receptor antagonism Anagnostaras et al 1999;Kim et al 1991;Morris et al 1986;Kawabe et al 1998) all three exhibit sexual dimorphism (Maren et al 1994b;Anagnostaras et al 1998;Williams and Meck 1991), and recent evidence indicates similar targeted mutations in mice disrupt these tasks (e.g., Lu et al 1997). The present report confirms that contextual fear conditioning, like the water (Hagan et al 1986) and radial (Levin et al 1990) mazes, is also sensitive to cholinergic disruption.…”

Section: Discussionmentioning

confidence: 97%

Scopolamine and Pavlovian Fear Conditioning in Rats Dose-Effect Analysis

Anagnostaras

Maren

Sage

et al. 1999

Neuropsychopharmacology

135

130

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Section: Discussionmentioning

confidence: 97%

Scopolamine and Pavlovian Fear Conditioning in Rats Dose-Effect Analysis

Anagnostaras

Maren

Sage

et al. 1999

Neuropsychopharmacology

135

130

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Section: Spatial Memorymentioning

confidence: 99%

“…The sex differences in rodents have generally been attributed to the organizational effects of androgens, since neonatal castration of males or administration of T to newborn females eliminates such sex differences (Isgor and Sengelaub, 2003). The aromatization of androgens to estrogens may be particularly important in the development of the sex difference, since neonatal administration of E2 masculinizes spatial ability in female rats (Williams et al, 1990;Williams and Meck, 1991 (Isgor and Sengelaub, 1998;Joseph et al, 1978).Hormonal influence on such behaviors, however, may not be solely organizational. Adult circulating androgens and estrogens can also affect certain aspects of spatial memory performance and these effects may, at least partially, be mediated through activation of ARs in adulthood (Gibbs, 2005;Sandstrom et al, 2006;Naghdi et al, 2001).…”

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confidence: 99%

The role of androgen receptors in the masculinization of brain and behavior: What we've learned from the testicular feminization mutation

Zuloaga

Puts

Jordan

et al. 2008

Hormones and Behavior

212

156

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Many studies demonstrate that exposure to testicular steroids such as testosterone early in life masculinizes the developing brain, leading to permanent changes in behavior. Traditionally, masculinization of the rodent brain is believed to depend on estrogen receptors (ERs) and not androgen receptors (ARs). According to the aromatization hypothesis, circulating testosterone from the testes is converted locally in the brain by aromatase to estrogens, which then activate ERs to masculinize the brain. However, an emerging body of evidence indicates that the aromatization hypothesis cannot fully account for sex differences in brain morphology and behavior, and that androgens acting on ARs also play a role. The testicular feminization mutation (Tfm) in rodents, which produces a nonfunctional AR protein, provides an excellent model to probe the role of ARs in the development of brain and behavior. Tfm rodent models indicate that ARs are normally involved in the masculinization of many sexually dimorphic brain regions and a variety of behaviors, including sexual behaviors, stress response and cognitive processing. We review the role of ARs in the development of the brain and behavior, with an emphasis on what has been learned from Tfm rodents as well as from related mutations in humans causing complete androgen insensitivity. Keywordscomplete androgen insensitivity syndrome -CAIS; vasopressin; anxiety; spatial memory; bed nucleus; medial amygdala; SDN-POA; sexual behavior; aggression; VMH Exposure to testicular steroids such as testosterone (T) early in life masculinizes the developing brain, leading to permanent changes in behavior in a wide variety of animal models (Morris et al., 2004). According to the aromatization hypothesis, T is converted by aromatase into 17-β estradiol (E2), which then acts on estrogen receptors (ERs) to masculinize the brain (Naftolin et al., 1975). Traditionally, aromatization is believed to be the mechanism by which the rodent brain becomes masculinized and defeminized. Some sexually dimorphic regions within the hypothalamus adhere well to this hypothesis, including the sexually dimorphic nucleus of the preoptic area (SDN-POA) and anteroventral periventricular nucleus (AVPV). T spares neuronsCorresponding author: Damian Zuloaga, Neuroscience Program, 108 Giltner Hall, Michigan State University, East Lansing, MI 48824, Phone: Fax: (517) 432-2744, Email: E-mail: zuloagad@msu.edu. Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. NIH Public Access NIH-PA Author ManuscriptNIH-PA Author Manuscript NIH-PA Author Manuscript from death in the SDN-POA...

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“…Testosterone treatment of females at birth alters the phenotype of the hypothalamic-pituitary-adrenal axis (Seale et al, 2005), the morphology of sexually dimorphic brain regions (Han and De Vries, 2003;MacLusky et al, 1987;Morris et al, 2004;Roselli and Klosterman, 1998) and affects certain aspects of learning (Roof, 1993;Roof and Havens, 1992;Shors and Miesegeas, 2002;Williams and Meck, 1991). Therefore, we were surprised that learned helplessness behavior did not emerge in females that were masculinized at birth.…”

Section: Sex Differences In Helplessnessmentioning

confidence: 99%

Females do not Express Learned Helplessness like Males do

Dalla

Edgecomb

Whetstone

et al. 2007

Neuropsychopharmacol

149

101

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Women are more likely than men to suffer from stress-related mental disorders, such as depression. In the present experiments, we identified sex differences in one of the most common animal models of depression, that of learned helplessness. Male and female rats were trained to escape a mild footshock each day for 7 days (controllable stress). Each rat was yoked to another rat that could not escape (uncontrollable stress), but was exposed to the same amount of shock. One day later, all stressed rats and unstressed controls were tested on a more difficult escape task in a different context. Most males exposed to uncontrollable stress did not learn to escape and were therefore helpless. In contrast, most females did learn to escape on the more difficult escape task, irrespective of whether they had been exposed to controllable or uncontrollable stress. The sex differences in helplessness behavior were not dependent on the presence of sex hormones in adulthood, because neither ovariectomy of females nor castration of males abolished them. The absence of helplessness in females was neither dependent on organizational effects of testosterone during the day of birth, because masculinized females did not express helplessness as adults. Thus, sex differences in helplessness behavior are independent of gonadal hormones in adulthood and testosterone exposure during perinatal development. Learned helplessness may not constitute a valid model for depressive behavior in women, at least as reflected by the response of female rats to operant conditioning procedures after stressful experience.

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The organizational effects of gonadal steroids on sexually dimorphic spatial ability

Cited by 408 publications

References 58 publications

Scopolamine and Pavlovian Fear Conditioning in Rats Dose-Effect Analysis

Scopolamine and Pavlovian Fear Conditioning in Rats Dose-Effect Analysis

The role of androgen receptors in the masculinization of brain and behavior: What we've learned from the testicular feminization mutation

Females do not Express Learned Helplessness like Males do

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