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

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).

Chronic administration of androgens with actions at estrogen receptor beta have anti-anxiety and cognitive-enhancing effects in male rats.

Androgen levels decline with aging. Some androgens may exert anti-anxiety and cognitive-enhancing effects; however, determining which androgens have anxiolytic-like and/or mnemonic effects is of interest given the different mechanisms that may underlie some of their effects. For example, the 5 alpha-reduced metabolite of testosterone (T), dihydrotesterone, can be further converted to 5 alpha-androstane,17beta-diol-3 alpha-diol (3 alpha-diol) and 5 alpha-androstane,17beta-diol-3beta-diol (3beta-diol), both of which bind with high affinity to the beta isomer of the intracellular estrogen receptor beta (ER beta).

Chronic administration of androgens with actions at estrogen receptor beta have anti-anxiety and cognitive-enhancing effects in male rats.

Androgen levels decline with aging. Some androgens may exert anti-anxiety and cognitive-enhancing effects; however, determining which androgens have anxiolytic-like and/or mnemonic effects is of interest given the different mechanisms that may underlie some of their effects. For example, the 5 alpha-reduced metabolite of testosterone (T), dihydrotesterone, can be further converted to 5 alpha-androstane,17beta-diol-3 alpha-diol (3 alpha-diol) and 5 alpha-androstane,17beta-diol-3beta-diol (3beta-diol), both of which bind with high affinity to the beta isomer of the intracellular estrogen receptor beta (ER beta).

Androgens with activity at estrogen receptor beta have anxiolytic and cognitive-enhancing effects in male rats and mice.

Testosterone (T) and its metabolites may underlie some beneficial effects for anxiety and cognition, but the mechanisms for these effects are unclear. T is reduced to dihydrotestosterone (DHT), which can be converted to 5alpha-androstane,3alpha,17beta-diol (3alpha-diol) and/or 5alpha-androstane-3beta,17beta-diol (3beta-diol). Additionally, T can be converted to androstenedione, and then to androsterone.

NorthEast Under/graduate Research Organization for Neuroscience (NEURON): Our Third New York City Meeting.

The NorthEast Under/graduate Research Organization for Neuroscience (N.E.U.

Androgen administration to aged male mice increases anti-anxiety behavior and enhances cognitive performance.

Although androgen secretion is reduced with aging, and may underlie decrements in cognitive and affective performance, the effects and mechanisms of androgens to mediate these behaviors are not well understood. Testosterone (T), the primary male androgen, is aromatized to estrogen (E(2)), and reduced to dihydrotestosterone (DHT), which is converted to 5alpha-androstane, 3alpha, 17beta-diol (3alpha-diol). To ascertain whether actions of the neuroactive metabolite of T, 3alpha-diol, mediates cognitive and affective behaviors, intact, aged male C57/B6 mice (24 month old) as well as young, intact and gonadectomized (GDX; 12 week old) mice were administered s.

Sexual experience of male rats influences anxiety-like behavior and androgen levels.

There is a wide body of literature to suggest that sexual experience may influence androgen secretion in various species, in turn, androgens may also influence anxiety. We hypothesized that sexual experience may alter anxiety behavior and secretion of endogenous androgens. Experiment 1: anxiety behavior of rats with a history of sexual experience was compared to that of sexually-inexperienced, naïve male rats.

Androgens' performance-enhancing effects in the inhibitory avoidance and water maze tasks may involve actions at intracellular androgen receptors in the dorsal hippocampus.

Androgens can have performance-enhancing effects in some cognitive tasks, but the mechanism of these effects has not been established. Experiments examined whether androgens' actions to bind to intracellular androgen receptors (ARs) in the hippocampus are necessary to enhance cognitive performance in the inhibitory avoidance and water maze tasks. If androgens' binding at ARs are essential, then blocking them through intrahippocampal administration of flutamide, an AR receptor antagonist, should attenuate androgens' performance-enhancing effects in the inhibitory avoidance and water maze tasks.

Androgens' effects to enhance learning may be mediated in part through actions at estrogen receptor-beta in the hippocampus.

Testosterone (T) may enhance cognitive performance. However, its mechanisms are not well understood. First, we hypothesized that if T's effects are mediated in part through actions of its 5alpha-reduced metabolites, dihydrotestosterone (DHT) and/or 3alpha-androstanediol (3alpha-diol) in the hippocampus, then T, DHT, and 3alpha-diol-administration directly to the hippocampus should enhance learning and memory in the inhibitory avoidance task.

Intrahippocampal administration of an androgen receptor antagonist, flutamide, can increase anxiety-like behavior in intact and DHT-replaced male rats.

Testosterone (T) and its 5alpha-reduced metabolite, dihydrotestosterone (DHT), can decrease anxiety-like behavior; however, the mechanisms underlying these effects have not been established. First, we hypothesized that if T reduces anxiety-like behavior through actions of its 5alpha-reduced metabolite, DHT, then gonadectomy (GDX) would increase anxiety-like behavior, an effect which would be reversed by systemic administration of DHT. Second, we hypothesized that if T and DHT reduce anxiety-like behavior in part through actions at intracellular androgen receptors in the hippocampus, then administration of an androgen receptor antagonist, flutamide, directly to the hippocampus should increase anxiety-like behavior of intact and DHT-replaced, but not GDX, male rats.

Testosterone's anti-anxiety and analgesic effects may be due in part to actions of its 5alpha-reduced metabolites in the hippocampus.

Although testosterone (T) may have effects to enhance analgesia and reduce anxiety, its effects and mechanisms are not well understood. We hypothesized that if T's anti-anxiety and analgesic effects are due in part to actions of its 5alpha-reduced metabolite (dihydrotestosterone-DHT) and/or its 3alpha-hydroxysteroid dehydrogenase reduced metabolite (3alpha-androstanediol-3alpha-diol), in the hippocampus, then androgen regimens that increase levels of these metabolites in the hippocampus should produce anti-anxiety behavior, and analgesic effects, in gonadectomized (GDX) male rats. In Experiment 1, GDX rats were administered T, DHT, 3alpha-diol (1 mg/kg, SC), or vehicle.

Testosterone's analgesic, anxiolytic, and cognitive-enhancing effects may be due in part to actions of its 5alpha-reduced metabolites in the hippocampus.

Although testosterone (T) may decrease anxiety and enhance cognitive performance, its mechanisms are not well understood. The authors hypothesized that if T's effects are mediated in part through actions of its 5alpha-reduced, nonaromatizable metabolite dihydrotestosterone (DHT) and/or its 3alpha-hydroxysteroid dehydrogenase reduced metabolite 3alpha-androstanediol (3alpha-diol) in the hippocampus, then T, DHT, and 3alpha-diol administration should produce similar behavioral effects concomitant with elevating T metabolites in the hippocampus. Gonadectomized male rats administered T, DHT, or 3alpha-diol via Silastic capsules or intrahippocampal infusions had greater analgesia (tail flick, paw lick), less anxiety behavior (plus-maze, open field, defensive freezing), and better learning (inhibitory avoidance) compared with vehicle control rats.

Mnemonic effects of testosterone and its 5alpha-reduced metabolites in the conditioned fear and inhibitory avoidance tasks.

Experiments were conducted to examine whether performance in hippocampally-mediated learning tasks is influenced by testosterone (T) and/or its 5alpha-reduced metabolites, dihydrotestosterone (DHT) and 3alpha-androstanediol (3alpha-diol). Performance in the conditioned fear and inhibitory avoidance tasks were examined in intact and gonadectomized (GDX), androgen-replaced rats. In Experiment 1, the behavior of intact and GDX rats in the conditioned fear paradigm were compared.

Testosterone's metabolism in the hippocampus may mediate its anti-anxiety effects in male rats.

Androgens may mediate anxiety behaviors; however, these effects and mechanisms of androgens are not well understood. The following experiments investigated whether testosterone (T)'s effects on anxiety behavior are mediated by its 5alpha-reduced, nonaromatizable metabolite dihydrotestosterone (DHT) and/or its 3alpha-hydroxysteroid dehydrogenase (3alpha-HSD) reduced metabolite 3alpha-androstanediol (3alpha-diol). In Experiment 1, gonadally-intact adult male rats and gonadectomized (GDX), DHT-replaced rats had similar low levels of anxiety behavior in the open field and elevated plus maze and fear behavior in the defensive freezing task compared with GDX control rats.

5alpha-reduced androgens may have actions in the hippocampus to enhance cognitive performance of male rats.

Androgens may improve cognitive performance; however, these effects and mechanisms of androgens are not well understood. Whether testosterone's (T) effects on cognitive performance are mediated by its 5alpha-reduced, non-aromatizable metabolite dihydrotestosterone (DHT) and/or its 3alpha-hydroxysteroid dehydrogenase (3alpha-HSD) reduced metabolite 3alpha-androstanediol (3alpha-diol), was investigated. In Experiment 1, male rats that were gonadally intact, or gonadectomized (GDX) and DHT-replaced with a silastic capsule, had better performance in the inhibitory avoidance task, and higher plasma DHT and 3alpha-diol levels, compared to GDX rats.

Northeast Under/graduate Organization for Neuroscience, A Regional Neuroscience Meeting for Undergraduates, Graduate Students, and Faculty.

The Northeast Under/graduate Organization for Neuroscience (N.E.U.