Testosterone ameliorates streptozotocin-induced memory impairment in male rats (original) (raw)
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DARU Journal of Pharmaceutical Sciences, 2012
Background and purpose of the study Recent studies demonstrate that androgens, beyond regulating sexual behavior, exert several neuroprotective functions in the brain. The present study was designed to explore effect of testosterone in memory impairment induced by intra- cerebroventricular (icv) injection of streptozotocin (STZ) as a model of sporadic AD. Methods Study was carried out on male Wistar rats. Animals were randomly divided into 11 equal groups. Experimental model of AD was induced by bilateral icv injection of STZ at the dose of 750 μg/Rat/10 μl ACSF at days 1 and 3. STZ-induced memory impairment was assessed two weeks after the last dose of STZ by using a passive avoidance task (1 mA). The interval between the placement of animals in the illuminated chamber and the entry into the dark chamber was measured as a step-through latency (STL). Castration was performed by surgical removing of testis and behavioral study of memory impairment was done after 4 weeks. Results Resu...
Iranian Journal of Pharmaceutical Research, 2005
Androgens have been shown to affect cognitive aspects of spatial memory. Testosterone which is the most important androgen, plays a role in the organization of behavior during development. Also, it has been shown that androgens cause sex related differences in learning and memory especially during neonatal period. In the current study, we assessed the effects of castration and testosterone enanthate (TE) administration on spatial cognition. Multiple doses of testosterone enanthate (20, 40, 80 and 120 mg/Kg) were examined on different groups using Morris water maze. Spatial memory was preserved in castrated rats. There was also no difference among multiple doses and control groups. For control of the level of testosterone in the blood of casterated rats and intact rats, blood samples were collected from intact group and 7, 10, 12, 14, 21 days after casteration. Testosterone levels were measured by Radio-immuno assay (RIA) technique and compared among all groups. The level of testoste...
Effects of testosterone and estrogen replacement on memory function
Menopause, 2010
Objective: Testosterone insufficiency has been associated with psychosexual problems, reduced psychological well-being, and negative metabolic consequences, whereas less is known about the effects on cognition. The aim of this study was to investigate the effect of adding testosterone to estrogen therapy on memory functions in oophorectomized women. Methods: In a randomized, double-blind, placebo-controlled design, women with surgically induced menopause (n = 50; mean [SD] age, 54.0 [2.9] y) received estradiol valerate in combination with testosterone undecanoate or placebo. The women were assessed with a self-report questionnaire regarding memory and neuropsychological tests for verbal and spatial episodic memory and incidental learning at baseline, at the time of crossover, and after completion of treatment. Results: Testosterone undecanoate 40 mg added to estrogen therapy had a negative effect on immediate but not delayed verbal memory at 24 weeks. Subjective and objective memory showed some correspondence as the women in the estrogen + placebo treatment group rated decreased everyday memory problems at 24 weeks compared with baseline. This was not observed in the women in the estrogen + testosterone treatment. Verbal attention span deteriorated from baseline with estrogen + placebo treatment but not with the estrogen + testosterone treatment. However, there was no significant treatment effect between the two groups. Conclusions: Adding testosterone to estrogen treatment deteriorated immediate verbal memory compared with estrogen + placebo, while other memory functions were unaffected.
Behavioural Brain Research, 2006
Neurohormones like testosterone and estrogen have an important role in learning and memory. Many biological effects of androgens in the brain require the local conversion of these steroids to an estrogen. The current research has conducted to assess the effect of testosterone, estrogen and aromatase inhibitor (anastrozole) on spatial discrimination of rats, using Morris water maze and also the pathway of the effect of testosterone by using anastrozole. Adult male rats were bilaterally cannulated into CA1 region of hippocampus and divided into 15 groups. Different groups received DMSO 0.5 l and DMSO 0.5 l + DMSO 0.5 l as control groups and different doses of testosterone enanthate (TE) (20, 40 and 80 g/0.5 l), estradiol valerat (EV) (1, 2.5, 5, 10, and 15 g/0.5 l), anastrozole (An) (0.25, 0.5, 1 g/0.5 l), TE 80 g/0.5 l + anastrozole 0.5 g/0.5 l and EV 15 g/0.5 l + anastrozole 0.5 g/0.5 l all days before training. TE and EV were injected 30-35 min before training and anastrozole was injected 25-30 min before training. Our results have shown both TE 80 g/0.5 l and EV 15 g/0.5 l groups increase in escape latency and traveled distance to find invisible platform. Also we have shown that anastrozole dose dependently decreases escape latency and traveled distance. We resulted that both TE and EN impaired acquisition of spatial learning and memory but anastrozole improved it. Anastrozole also could be buffered TE-induced impairment effect but not EV. (N. Naghdi). modulation on mnemonic processes . Testosterone, and its metabolite estradiol, appears to mediate spatial learning and memory performance both organizationally and possibly activationally . The literature of androgen effects on spatial memory in adult animal and humans is complex and contradictory. Some evidence suggests a positive correlation between testosterone and spatial ability . Some studies have suggested that testosterone or its metabolites to the hippocampus can improve spatial memory . There is also general consensus that men outperform women in tasks that require spatial skills . In the other hand, in adult human tested for spatial ability, men who had the lowest levels of salivary testosterone performed the best . Several reports also indicated that chronic treatment with androgenic compounds has impaired spatial learning and retention of spatial information in young and middle-aged animals and human . Further, the role of steroid hormones in learning and memory were 0166-4328/$ -see front matter
Current Psychopharmacology, 2014
Although there are therapeutic applications of the Anabolic Androgenic Steroids (AAS), the predominant use implies the illicit self-administration by athletes and adolescents. In this respect, AAS abuse is associated with untoward effects on brain and behavior. Exposure to supraphysiological doses of AAS leads to changes in anxiety and aggression, but their effects on cognitive functions are poorly understood. We investigated the effects of the AAS testosterone propionate (TP), acutely or chronically administered in supraphysiological doses, on memory in rats. Experiment I-Adult male Wistar rats were treated once with vehicle (Control group, n = 5) or TP (10 mg/kg, n = 5). Behavioral experiments were performed 60 minutes after the single injection, and included the evaluation of spatial working memory and recognition memory. Experiment II-The rats received repeated daily administration of vehicle (n = 6) or TP (n = 7) for 40 days. Behavioral experiments started 23 hours after the last injection. After behavioral procedures, the animals were euthanized, the blood was collected for biochemical analyses and testicles were removed and weighted. Regarding the behavioral assessment, rats chronically treated with TP presented decreased time exploring the novel object when compared to control group. Rats that were treated acutely showed no significant difference compared with control. Acute or chronic treatments with TP were not effective in promoting changes in spatial working memory. Additionally, chronic treatment with TP induced significantly increases in biochemistry marker the enzyme glutamate pyruvate transaminase (SGPT) and a reduction in testicular weight as compared with control. Even though not interfering with spatial working memory performance, AAS abuse could induce deficit on recognition memory.
Effects of testosterone on spatial learning and memory in adult male rats
Hormones and Behavior, 2011
A male advantage over females for spatial tasks has been well documented in both humans and rodents, but it remains unclear how the activational effects of testosterone influence spatial ability in males. In a series of experiments, we tested how injections of testosterone influenced the spatial working and reference memory of castrated male rats. In the eight-arm radial maze, testosterone injections (0.500 mg/rat) reduced the number of working memory errors during the early blocks of testing but had no effect on the number of reference memory errors relative to the castrated control group. In a reference memory version of the Morris water maze, injections of a wide range of testosterone doses (0.0625-1.000 mg/rat) reduced path lengths to the hidden platform, indicative of improved spatial learning. This improved learning was independent of testosterone dose, with all treatment groups showing better performance than the castrated control males. Furthermore, this effect was only observed when rats were given testosterone injections starting seven days prior to water maze testing and not when injections were given only on the testing days. We also observed that certain doses of testosterone (0.250 and 1.000 mg/rat) increased perseverative behavior in a reversal-learning task. Finally, testosterone did not have a clear effect on spatial working memory in the Morris water maze, although intermediate doses seemed to optimize performance. Overall, the results indicate that testosterone can have positive activational effects on spatial learning and memory, but the duration of testosterone replacement and the nature of the spatial task modify these effects.
Testosterone modulates performance on a spatial working memory task in male rats
Hormones and Behavior, 2006
Gonadal hormones have been shown to modulate memory retention in female rats. The current experiments examine the role of testicular hormones in modulating the performance of male rats on two spatial water maze tasks. In the first study, castrated and intact rats were trained on the visible platform and hidden platform versions of the Morris water maze task. Castration did not affect performance on either version of this reference memory task with castrated and intact rats demonstrating similar performance both during acquisition and on post-training probe trials. In the second experiment, castrated and intact rats were tested on a delayed-matching-to-place version of the water maze. Rats received a series of trial pairs in the maze with a hidden platform located in the same pool location on the exposure and retention trials of each pair; between pairs of trials, however, the platform was repositioned to a novel pool location. The interval between trials was either 10-or 60-min and memory retention, taken as the difference between the pathlengths on the exposure and retention trials, declined as the interval increased. Relative to intact males, castrated males demonstrated impaired working memory retention at 60-min but not at 10-min retention intervals. This interval-dependent impairment in working memory retention was reversed by physiologic levels of testosterone replacement. These findings indicate that castration does not significantly affect acquisition or probe trial performance on a classic reference memory task but does impair spatial working memory retention, an effect that is reversed by exogenous testosterone.
Bulletin of Egyptian Society for Physiological Sciences, 2010
The study aimed to test whether the decrease in testosterone level during aging is the underlying mechanism for the deterioration in memory and cognitive functions. This was achieved through determination of hippocampal neurotransmission by in vivo determination of extracellular dopamine and serotonin in CA1 hippocampal region and brain derived neurotorphic factor (BDNF) synthesis in both normal and unilateral castrated rats (an experimental model for hypogonadism) and 2 and 4 days after single dose of exemestane (5mg/kg, p.o.). In addition, learning and memory processes were determined using Morris water maze. Results showed that unilateral castration resulted in significant decrease in testosterone level, disturbing the testosterone/estradiol ratio and enhanced hippocampal neurotransmission. Besides, these effects were accompanied with an enhanced learning and memory and significant decrease in the level of BDNF expression. Whereas, exemestane treatment increased testosterone level and inhibited DA and 5-HT release, significantly increased BDNF expression and inhibited learning and memory processes in both normal and unilateral castrated groups. The study indicated that moderate hypogonadism has a positive effect on hippocampal neurotransmission, learning and memory due to the imbalance of testosterone/estradiol in favor of estradiol. On the other hand, exemestane effects might be due to imbalance of testosterone/estradiol ratio in favor of testosterone. In addition, it seems that the beneficial effects of physiological levels of testosterone are indirectly due its conversion to estradiol. Moreover, the study indicated that moderate decline in endogenous testosterone in healthy aged individuals is not the underlying mechanism of the age-related deterioration in the cognitive function.
Behavioural Brain Research, 2008
The hippocampus is essentially involved in learning and memory, and is known to be a target for androgen actions. Androgen receptors are densely expressed in CA1 of rat hippocampus, and mediate the effects of testosterone (T) on learning and memory. T depletion or administration can modulate neural function and cognitive performance. We conducted series of experiments to further investigate the effect of castration or intra hippocampal injection of T on acquisition, consolidation and retrieval of inhibitory avoidance learning and memory. Male adult rats were bilaterally cannulated into CA1 of hippocampus, and then received T (1, 10, 20, 40 and 80 g/0.5 l/side) or vehicle (DMSO), 30 min before training, immediately after training and 30 min before retrieval in inhibitory avoidance task. Castration was made by gonadectomy of male rats and behavioral tests performed 4 weeks later. Our results showed that gonadectomy of male rats did not influence performance on inhibitory avoidance task, as compared to sham-operated rats. We have also found that pre-training, post-training and pre-retrieval intra CA1 injections of T significantly decreased step-through latencies in inhibitory avoidance learning at doses 1 and 80, 20, and 20 and 40 g/0.5 l/side, respectively. The data suggest that intra CA1 administration of T could impair learning and memory acquisition, consolidation and retrieval, while systemic androgen's depletion have no effect on memory, in inhibitory avoidance task.
Age-dependent effects of testosterone on spatial memory in male rats
Hormones and Behavior, 2020
Decreased spatial memory is common in aging populations and reduces their quality of life. Although its role is still controversial, low testosterone (T) may contribute to impaired cognition in aged men. This study aimed to identify the role of T in age-related deficiencies in spatial memory among male rats. Young adult (3 months old) and aged (21 months old) Wistar rats were assigned to independent groups: intact, orchidectomized, or orchidectomized + subcutaneous pellets of T propionate. The phases of spatial memory acquisition (4 daily trials/ 4 days) and spatial memory retention (1 trial/day, 3 and 12 days after acquisition) were evaluated using the Barnes maze. Compared with young adults, aged intact rats took longer to find the goal, made more mistakes, and showed only slight improvements in goal sector exploration across the acquisition period. The young orchidectomized rats showed no improvement in performance over the days during the acquisition phase. T treatment in hormonally deprived old rats produced a small improvement in goal sector exploration and number of errors during the acquisition phase. Meanwhile, in young adults, this treatment improved the goal sector searching in the retention phase (12 days after acquisition training). Our results suggested that age-related spatial memory deficits cannot be entirely explained by the decline in T levels; however, this androgen produced subtle and mild beneficial effects on spatial memory in young and old males. Taken together, our findings suggest age differences in the role of T on spatial memory in males.