Intrahippocampal Injection of 3α Diol (a Testosterone Metabolite ) and Indomethacin (3α-HSD Blocker), Impair Acquisition of Spatial Learning and Memory in Adult Male Rats (original) (raw)
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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
Iranian biomedical journal, 2012
Testosterone and its metabolites have important roles in learning and memory. The current study has conducted to assess the effect of pre-training, post-training and pre-probe trial intrahippocampal CA1 administration of 3α-anderostanediol (one of the metabolites of testosterone) and indomethacin (as 3α-hydroxysteroid dehydrogenase enzyme blocker) on acquisition, consolidation and retrieval in Morris water maze (MWM) task. Adult male rats were bilaterally cannulated into CA1 region of hippocampus and then received 3α-diol (0.2, 1, 3 and 6 mug/0.5 mul/side), indomethacin (1.5, 3 and 6 mug/0.5 mul/side), indomethacin (3 mug/0.5 mul/side) + 3α-diol (1 mug/0.5 mul/side), 25-35 min before training, immediately after training and 25-35 min before probe trial in MWM task. Our results showed that injection of 3α-diol and indomethacin significantly increased the escape latency and traveled distance to find hidden platform in acquisition and consolidation stage, but did not have any effect on...
Iranian Journal of Pharmaceutical Research : IJPR, 2012
CA1 region of hippocampus has an important role in learning and memory. Previous reports have shown that androgens like testosterone and its metabolites are present in high concentration in CA1 region of hippocampus. Androgen receptors have also high density in this region. Therefore, it is suggested that neurohormones in CA1 have an important role in learning and memory. It is likely that testosterone exerts its effect via its metabolites, especially dihydrotestosterone (DHT), a 5α-reduced androgen. In this research, we conducted an experiment to assess the path of testosterone›s effectiveness on spatial learning and memory. Adult male rats were randomly divided into 4 groups and, bilaterally, cannulated into CA1 region of hippocampus. One week after the surgery, animals received DMSO 0.5 μL as a control group and different doses of dihydrotestosterone (DHT) (0.25, 0.5 and 1 µg/0.5 μL/side) 25-30 min before the training in spatial version of Morris Water Maze task. Training session...
Behavioural Brain Research, 2005
In most mammals, the hippocampus has a well-documented role in spatial memory acquisition. High concentration of androgen receptors in fundamental centers of learning and memory in brain such as hippocampus shows that there may be some relationships between androgen receptors and cognitive aspects of brain. Previous studies, which have shown sex-dependent differences in hippocampal morphology and physiology, suggest a modulatory role for sex steroids in hippocampal function. Androgens have been shown to modulate some hippocampalmediated behaviors including learning and memory. To study the mechanism of action of androgens in processes underlying learning and memory, anisomycin, a protein synthesis inhibitor was used to prevent the genomic effects of testosterone. Therefore, the effects of anisomycin and testosterone together were assessed on rat's performance in MWM. Rats received anisomycin (2.5 g/0.5 l), testosterone (80 g/0.5 l) or both anisomycin (2.5 g/0.5 l) and testosterone (80 g/0.5 l) through the connulas in the CA1 region. Anisomycin was injected 20 min and testosterone was injected 35 min before training each day. The results showed that anisomycin (2.5 g/0.5 l) and testosterone (80 g/0.5 l) increased latencies to find the invisible platform. But the group that received testosterone and anisomycin together was decrease in latency and traveled distance to find the invisible platform.
Effect of spatial learning on hippocampal testosterone in intact and castrated male rats
Iranian biomedical journal, 2009
Sex steroids and their receptors exist in hippocampus and affect spatial learning and memory. This study was designed to measure testosterone level of CA1 and to assess the effect of spatial learning on its amount in left and right hippocampus of adult male rats. Sixteen rats were divided into two intact and castrated groups, and then trained in Morris water maze (MWM). Another 40 animals were divided into four groups and their right or left hippocampus cannulated. Half of the animals in each group were castrated simultaneously. All the animals were trained in MWM. Microdialysis was performed and steroid contents of hippocampal dialysate were analyzed through HPLC/ultraviolet detection device method. Results showed no significant differences between control and castrated animals in spatial learning after four days of training. Gonadectomy did not change testosterone level in CA1 region of hippocampus. Spatial learning decreased testosterone levels in CA1 region of hippocampus in rig...
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.
Neurobiology of Learning and Memory, 2007
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 5α-reduced metabolites, dihydrotestosterone (DHT) and/or 3α-androstanediol (3α-diol) in the hippocampus, then T, DHT, and 3α-diol-administration directly to the hippocampus should enhance learning and memory in the inhibitory avoidance task. In order to test this hypothesis, gonadectomized (GDX) male rats were administered T, DHT, or 3α-diol via intrahippocampal inserts immediately following training in the inhibitory avoidance task. We found that T tended to increase, and DHT and 3α-diol significantly increased, performance in the inhibitory avoidance task compared to vehicle-administered GDX rats. Second, we hypothesized that, if androgens' effects are due in part to actions of 3α-diol in the hippocampus, then systemic or intrahippocampal administration of 3α-diol should significantly enhance cognitive performance of GDX male rats. Third, we hypothesized that, if androgen metabolites can have actions at estrogen receptors (ERs) in the hippocampus, then administration of ER antisense oligonucleotides (AS-ODNs) directly to the hippocampus of GDX, 3α-diol replaced, rats would decrease learning in the inhibitory avoidance task. We found that intrahippocampal administration of AS-ODNs for ERβ, but not ERα, significantly decreased learning and memory of 3α-diol replaced rats. Together, these findings suggest that T's effects to enhance learning and memory may take place, in part, through actions of its metabolite, 3α-diol, at ERβ in the dorsal hippocampus.
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.
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...