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3alpha-androstanediol, but not testosterone, attenuates age-related decrements in cognitive, anxiety, and depressive behavior of male rats.

Frye CA, Edinger KL, Lephart ED, Walf AA - Front Aging Neurosci (2010)

Bottom Line: Testosterone (T) is aromatized to estrogen, and reduced to dihydrotestosterone (DHT), which is converted to 5alpha-androstane, 3alpha, 17alpha-diol (3alpha-diol).There was age-related decline in performance of the inhibitory avoidance, water maze, defensive freezing, and forced swim tasks, and hippocampal 3alpha-diol levels.Experiments 2 and 3 assessed whether acute subcutaneous T or 3alpha-diol, respectively, could reverse age-associated decline in performance. 3alpha-diol, but not T, compared to vehicle, improved performance in the inhibitory avoidance, water maze, forced swim, and defensive freezing tasks, irrespective of age.

View Article: PubMed Central - PubMed

Affiliation: Department of Psychology, University at Albany-SUNY Albany, NY, USA.

ABSTRACT
Some hippocampally-influenced affective and/or cognitive processes decline with aging. The role of androgens in this process is of interest. Testosterone (T) is aromatized to estrogen, and reduced to dihydrotestosterone (DHT), which is converted to 5alpha-androstane, 3alpha, 17alpha-diol (3alpha-diol). To determine the extent to which some age-related decline in hippocampally-influenced behaviors may be due to androgens, we examined the effects of variation in androgen levels due to age, gonadectomy, and androgen replacement on cognitive (inhibitory avoidance, Morris water maze) and affective (defensive freezing, forced swim) behavior among young (4 months), middle-aged (13 months), and aged (24 months) male rats. Plasma and hippocampal levels of androgens were determined. In experiment 1, comparisons were made between 4-, 13-, and 24-month-old rats that were intact or gonadectomized (GDX) and administered a T-filled or empty silastic capsule. There was age-related decline in performance of the inhibitory avoidance, water maze, defensive freezing, and forced swim tasks, and hippocampal 3alpha-diol levels. Chronic, long-term (1-4 weeks) T-replacement reversed the effects of GDX in 4- and 13-month-old, but not 24-month-old, rats in the inhibitory avoidance task. Experiments 2 and 3 assessed whether acute subcutaneous T or 3alpha-diol, respectively, could reverse age-associated decline in performance. 3alpha-diol, but not T, compared to vehicle, improved performance in the inhibitory avoidance, water maze, forced swim, and defensive freezing tasks, irrespective of age. Thus, age is associated with a decrease in 3alpha-diol production and 3alpha-diol administration reinstates cognitive and affective performance of aged male rats.

No MeSH data available.


Represents hippocampal levels of T (A), E2 (B), DHT (C), and 3α-diol (D) in of 4- (black bars), 13- (dark grey bars), and 24- (light grey bars) month-old rats that were left intact (solid bars), GDX (white bars), or GDX and T-replaced (striped bars). * over individual bars denotes significant difference (p < 0.05) of GDX rats compared to intact rats (p < 0.05). * over brackets denotes difference at that age group compared to age groups that do not have a bracket above bars (p < 0.05).
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Figure 2: Represents hippocampal levels of T (A), E2 (B), DHT (C), and 3α-diol (D) in of 4- (black bars), 13- (dark grey bars), and 24- (light grey bars) month-old rats that were left intact (solid bars), GDX (white bars), or GDX and T-replaced (striped bars). * over individual bars denotes significant difference (p < 0.05) of GDX rats compared to intact rats (p < 0.05). * over brackets denotes difference at that age group compared to age groups that do not have a bracket above bars (p < 0.05).

Mentions: A main effect of age on swimming [F(2,129 = 14.90, p < 0.01] revealed more swimming among 4-month-old rats, compared to 13- (p < 0.01) and 24-month (p < 0.01) old rats. There was also a main effect of androgen condition on swimming [F(4,129) = 10.45, p < 0.01], such that, compared to intact rats, GDX (p < 0.01) rats spent significantly more time swimming. There was a significant interaction of age and androgen condition [F(4,129) = 2.02, p = 0.02], with GDX decreasing swimming in 4- and 13-, but not 24-, month-old, rats, compared to intact rats.


3alpha-androstanediol, but not testosterone, attenuates age-related decrements in cognitive, anxiety, and depressive behavior of male rats.

Frye CA, Edinger KL, Lephart ED, Walf AA - Front Aging Neurosci (2010)

Represents hippocampal levels of T (A), E2 (B), DHT (C), and 3α-diol (D) in of 4- (black bars), 13- (dark grey bars), and 24- (light grey bars) month-old rats that were left intact (solid bars), GDX (white bars), or GDX and T-replaced (striped bars). * over individual bars denotes significant difference (p < 0.05) of GDX rats compared to intact rats (p < 0.05). * over brackets denotes difference at that age group compared to age groups that do not have a bracket above bars (p < 0.05).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2874398&req=5

Figure 2: Represents hippocampal levels of T (A), E2 (B), DHT (C), and 3α-diol (D) in of 4- (black bars), 13- (dark grey bars), and 24- (light grey bars) month-old rats that were left intact (solid bars), GDX (white bars), or GDX and T-replaced (striped bars). * over individual bars denotes significant difference (p < 0.05) of GDX rats compared to intact rats (p < 0.05). * over brackets denotes difference at that age group compared to age groups that do not have a bracket above bars (p < 0.05).
Mentions: A main effect of age on swimming [F(2,129 = 14.90, p < 0.01] revealed more swimming among 4-month-old rats, compared to 13- (p < 0.01) and 24-month (p < 0.01) old rats. There was also a main effect of androgen condition on swimming [F(4,129) = 10.45, p < 0.01], such that, compared to intact rats, GDX (p < 0.01) rats spent significantly more time swimming. There was a significant interaction of age and androgen condition [F(4,129) = 2.02, p = 0.02], with GDX decreasing swimming in 4- and 13-, but not 24-, month-old, rats, compared to intact rats.

Bottom Line: Testosterone (T) is aromatized to estrogen, and reduced to dihydrotestosterone (DHT), which is converted to 5alpha-androstane, 3alpha, 17alpha-diol (3alpha-diol).There was age-related decline in performance of the inhibitory avoidance, water maze, defensive freezing, and forced swim tasks, and hippocampal 3alpha-diol levels.Experiments 2 and 3 assessed whether acute subcutaneous T or 3alpha-diol, respectively, could reverse age-associated decline in performance. 3alpha-diol, but not T, compared to vehicle, improved performance in the inhibitory avoidance, water maze, forced swim, and defensive freezing tasks, irrespective of age.

View Article: PubMed Central - PubMed

Affiliation: Department of Psychology, University at Albany-SUNY Albany, NY, USA.

ABSTRACT
Some hippocampally-influenced affective and/or cognitive processes decline with aging. The role of androgens in this process is of interest. Testosterone (T) is aromatized to estrogen, and reduced to dihydrotestosterone (DHT), which is converted to 5alpha-androstane, 3alpha, 17alpha-diol (3alpha-diol). To determine the extent to which some age-related decline in hippocampally-influenced behaviors may be due to androgens, we examined the effects of variation in androgen levels due to age, gonadectomy, and androgen replacement on cognitive (inhibitory avoidance, Morris water maze) and affective (defensive freezing, forced swim) behavior among young (4 months), middle-aged (13 months), and aged (24 months) male rats. Plasma and hippocampal levels of androgens were determined. In experiment 1, comparisons were made between 4-, 13-, and 24-month-old rats that were intact or gonadectomized (GDX) and administered a T-filled or empty silastic capsule. There was age-related decline in performance of the inhibitory avoidance, water maze, defensive freezing, and forced swim tasks, and hippocampal 3alpha-diol levels. Chronic, long-term (1-4 weeks) T-replacement reversed the effects of GDX in 4- and 13-month-old, but not 24-month-old, rats in the inhibitory avoidance task. Experiments 2 and 3 assessed whether acute subcutaneous T or 3alpha-diol, respectively, could reverse age-associated decline in performance. 3alpha-diol, but not T, compared to vehicle, improved performance in the inhibitory avoidance, water maze, forced swim, and defensive freezing tasks, irrespective of age. Thus, age is associated with a decrease in 3alpha-diol production and 3alpha-diol administration reinstates cognitive and affective performance of aged male rats.

No MeSH data available.