Testosterone and estradiol produce different effects on cognitive performance in male rats

Gibbs, Robert G.

doi:10.1016/j.yhbeh.2005.03.005

Cited by 100 publications

(101 citation statements)

References 61 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Such differences may account for the discrepancies here. So far, our studies have not detected any significant effects of gonadectomy or gonadal hormone treatment on acquisition of the CA task (Gibbs, 2005;Gibbs and Gabor, 2003); however, the possibility of a sex difference on this task with respect to the effects of cholinergic lesions cannot be excluded. Third, in the present study, all rats underwent training on the DMP task before being trained on the CA task.…”

Section: Effects On Ca Acquisitioncontrasting

confidence: 63%

See 1 more Smart Citation

Cholinergic lesions produce task-selective effects on delayed matching to position and configural association learning related to response pattern and strategy

Gibbs

Johnson

2007

Neurobiology of Learning and Memory

View full text Add to dashboard Cite

Abstract192 IgG-saporin (SAP) was used to selectively destroy cholinergic neurons in the rostral basal forebrain (e.g., medial septum (MS) and vertical limb of the diagonal band of Broca (VDB)) and/or the caudal basal forebrain (e.g., nucleus basalis magnocellularis (NBM)) of ovariectomized SpragueDawley rats. The effects of these lesions on two different cognitive tasks, a delayed matching to position (DMP) T-maze task, and a configural association (CA) operant conditioning task, were evaluated and compared. Injecting SAP into either the MS or NBM significantly impaired acquisition of the DMP task. Analysis showed that the effects were due largely to an affect on response patterns adopted by the rats during training, as opposed to an effect on working memory performance. Notably, the impairment in DMP acquisition did not correlate with the degree of cholinergic denervation of the hippocampus. Despite the deficit, most animals eventually learned the task and reached criterion; however by the end of training, controls and animals that received SAP into either the MS or NBM appeared more likely to use an allocentric place strategy to solve the task, whereas animals that received SAP into both the MS and NBM were more likely to use an egocentric response strategy. Cholinergic lesions also produced a small but significant affect on acquisition of the CA task, but only with respect to response time, and only in the SAP-NBM-treated animals. SAP-NBM lesions also produced small but significant impairments in both the number of responses and response time during the acquisition of simple associations, possibly reflecting an effect on alertness or attention. Notably, the effects on CA acquisition were small, and like the effects on DMP acquisition did not correlate with the degree of cholinergic denervation of the hippocampus. We conclude that selective basal forebrain cholinergic lesions produce learning deficits that are task specific, and that cholinergic denervation of either the frontal cortex or hippocampus can affect response patterns and strategy in ways that affect learning, without necessarily reflecting deficits in working memory performance.

show abstract

Section: Effects On Ca Acquisitioncontrasting

confidence: 63%

“…At the completion of DMP testing, rats were trained on an operant configural association (CA) negative patterning task as previously described (Butt, Allen, Arthur, Noble, Rea, and Rogers, 2000;Gibbs, 2005). Training was performed in operant chambers (Med.…”

Section: Ca Trainingmentioning

confidence: 99%

Cholinergic lesions produce task-selective effects on delayed matching to position and configural association learning related to response pattern and strategy

Gibbs

Johnson

2007

Neurobiology of Learning and Memory

View full text Add to dashboard Cite

show abstract

“…This is supportive of data showing an increase in BDNF mRNA in the dentate granule cell layer 53 hrs after an acute injection of estrogen (57). Numerous studies indicate that both estradiol and BDNF enhance hippocampal-dependent learning in male rats (50,45,37,54). Moreover, BDNF attenuates the impairing effects of stress on hippocampal dependent memory and LTP (11).…”

supporting

confidence: 86%

“…However, the literature does suggest that estradiol can enhance cognitive performance in male rodents and humans [37][38][39][43][44][45]. Intrahippocampal estradiol administration enhances memory consolidation in both male and female rats [44,45].…”

mentioning

confidence: 99%

Viral vector-mediated blockade of the endocrine stress–response modulates non-spatial memory

Ferguson

Lin

Sapolsky

2008

Neuroscience Letters

View full text Add to dashboard Cite

Stress results in the release of glucocorticoids (GCs) which, at high levels, impair hippocampusdependent tasks. Estrogen is neurotrophic and can rescue stress-induced memory impairments. Here we report the use of a viral-vector to overexpress a chimeric gene (ER/GR) that converts the deleterious effects of glucocorticoids into beneficial estrogenic effects. A short immobilization stress regimen was sufficient to impair non-spatial memory. In contrast, viral vector-mediated overexpression of ER/GR in the dentate gyrus of the hippocampus protected against stress-induced impairments of non-spatial memory. These data add to the growing evidence that increasing estrogenic signaling can protect against the impairing effects of stress on non-spatial memory.Hippocampal memory is sensitive to glucocorticoids (GCs, the adrenal steroids secreted during stress) in an inverted-U manner, such that low to moderate GC concentrations enhance hippocampal function, whereas abnormally low or the high levels associated with major stressors impair function [1,7]. In contrast to these detrimental effects of GCs, systemic and intrahippocampal estradiol administration can enhance performance in males and females in spatial and non-spatial memory tasks [8,9,[43][44][45]. Moreover, estrogen rescues both spatial and non-spatial memory from stress-induced learning impairments [20,21].Here we report a viral vector gene delivery strategy to express a chimeric receptor (ER/GR) that converts the deleterious effects of GCs into protective estrogenic effects. ER/GR is a modular chimeric gene that consists of the C-terminal hormone-binding domain of the glucocorticoid receptor and the N-terminal DNA-binding domain of the primary human estrogen receptor ERα [6,2]. ER/GR, when expressed, has the dual effects of competing with endogenous GR for GCs and converting GR-mediated signaling into neurotrophic ER responses [6]. In this study, we assessed if expression of ER/GR in the dentate gyrus could block the disruptive effects of stress on non-spatial memory. The construction of the ER/GR amplicon vector has been previously described [6]. Briefly, for stereotaxic infusion of vector, rats were anesthetized with 1ml/kg of a mixture consisting of 100 mg/kg ketamine, 10 mg/kg acepromazine, and 100 mg/kg xylazine. ER/GR or a control vector, expressing only a reporter gene GFP, were infused using a Hamilton syringe (Hamilton Company, Reno, NV) with a 28-gauge needle (1 ul over a 5 min period with a titer of 1× l0^6) dorsal to the apex of the dentate gyrus (DG) (coordinates: anteroposterior, 4 mm from bregma; mediolateral, 3.00 from midline;

show abstract

“…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). To further explore the role of ARs in spatial memory, performance in the MWM has been examined in both the rat and mouse Tfm models.…”

Section: Spatial Memorymentioning

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

213

156

View full text Add to dashboard Cite

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...

show abstract

Testosterone and estradiol produce different effects on cognitive performance in male rats

Cited by 100 publications

References 61 publications

Cholinergic lesions produce task-selective effects on delayed matching to position and configural association learning related to response pattern and strategy

Cholinergic lesions produce task-selective effects on delayed matching to position and configural association learning related to response pattern and strategy

Viral vector-mediated blockade of the endocrine stress–response modulates non-spatial memory

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

Contact Info

Product

Resources

About