Intrahippocampal injection of 3 alpha diol [a testosterone metabolite] and indomethacin [3 alpha -HSD blocker], impair acquisition of spatial learning and memory in adult male rats

Hippocampus is essentially involved in learning and memory processes, and is known to be a target for androgen actions. The high density of the androgen receptors in hippocampus shows that there must be some relationship between androgens and memory. Androgen effects on spatial memory are complex and contradictory. Some evidence suggests a positive correlation between androgens and spatial memory. While some other reports indicated an impairment effect. The present study was conducted to assess the effect of 3 alpha diol on spatial discrimination of rats. Adult male rats were bilaterally cannulated into CA1 region of hippocampus and then received 3 alpha diol [0.2, 1, 3 and 6 micro g/ 0.5 micro L/side], indomethacin [1.5, 3 and 6 micro g/ 0.5 micro L/side], indomethacin [3 micro g/ 0.5 micro L/side] + 3 alpha diol [1 micro g/ 0.5 micro L/side], 25-35 min before training in Morris Water Maze task. Our results showed that injection of 3 alpha diol [1, 3 and 6 micro g/ 0.5 micro L/side] and indomethacin [3 and 6 micro g/ 0.5 micro L/side] significantly increased the escape latency and traveled distance to find hidden platform. It is concluded that intra CA1 administration of 3 alpha diol and indomethacin could impair spatial learning and memory in acquisition stage. However, intra hippocampal injection of indomethacin plus 3 alpha diol could not change spatial learning and memory impairment effect of indomethacin or 3 alpha diol in Morris Water Maze task

Effect of 3alpha-anderostanediol and indomethacin on acquisition, consolidation and retrieval stage of spatial memory in adult male rats

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 3alpha-anderostanediol [one of the metabolites of testosterone] and indomethacin [as 3alpha-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 3alpha-diol [0.2, 1, 3 and 6 microg/0.5 microl/side], indomethacin [1.5, 3 and 6 microg/0.5 microl/side], indomethacin [3 microg/0.5 microl/side] + 3alpha-diol [1 microg/0.5 microl/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 3alpha-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 retrieval of spatial learning as compared with the control group. It is concluded that intra-CAl administration of 3alpha-diol and indomethacin could impair spatial learning and memory in acquisition and consolidation stage. Also, intrahippocampal injection of indomethacin + 3alpha-diol could not change spatial learning and memory impairment effect of indomethacin or 3a-diol in MWM task

Microinjection of dihydrotestosterone as a 5 alpha-reduced metabolite of testosterone into CA1 region of hippocampus could improve spatial learning in the adult male rats

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 5alpha-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 microL as a control group and different doses of dihydrotestosterone [DHT] [0.25, 0.5 and 1 microg/0.5 microL/side] 25-30 min before the training in spatial version of Morris Water Maze task. Training session contained two blocks which animals had to learn the position of hidden platform in 4 trials. On the test session [next day], rats performed a one-trial probe test and then a visible platform one. The results showed that escape latency and traveled distance were decreased significantly in DHT-treated [0.5 microg/0.5 microL/side] rats. This finding suggested that DHT may have improved the effect on acquisition of spatial learning and memory

effects of lidocaine reversible inactivation of the dorsal raphe nucleus on passive avoidance learning in rats

Introduction: The role of serotonergic fibers in avoidance learning is controversial. Involvement of the dorsal raphe nucleus [DRN], the main source of hippocampal projecting serotonergic fibers in acquisition, consolidation and retrieval of passive avoidance [PA] learning, was investigated by functional suppression of this area. Materials and Methods: DRN functional inactivation was done by lidocaine [0.5µl, 2%] injection into the DRN, 5 min before training [n=10]; and 5 [n=9], 90 [n=10] and 360 min [n=9] after acquisition trial. In the last experiment, lidocaine was injected into the DRN 5 min before the retrieval test, which was 48 h after the training [n=10]. Results: Our results showed that PA learning was not impaired by DRN inactivation 5 min before training nor 5 and 360 min after training. Lidocaine injected 90 min after the acquisition trial significantly reduced avoidance of the dark compartment [P<0.001]. Intra-DRN injection of lidocaine before retrieval significantly increased PA retention [P<0.001]. Therefore, it seems that DRN has opposite effects on consolidation and retrieval of passive avoidance learning, but it has no effect on PA acquisition. Discussion: It is suggested that functional ablation of DRN may disrupt integrity of subcortical circuits participating in PA consolidation, but DRN inactivation by increasing brain awareness may affect PA retrieval in rats

No significant difference between intact and testosteron depleted or administrated male rats in spatial learning and memory

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 testosterone after 7 days in casterated rats were 0 nmol/L and after 21 days were 0.02 +/- 0.02 nmol/L while in intact rats were 2.69 +/- 0.88 nmol/L. These data suggests that changes in the level of androgen in circulation have no effect on spatial localization, at least after puberty in male rats

Effects of citalopram on learning and memory in the mouse and rat

Data on the effects of serotonin reuptake inhibitors on learning and memory processes are not consistent. In the present study, the effects of citalopram, a very potent and completely selective inhibitor of the serotonin reuptake on spatial discrimination in the T-maze and Morris water maze, were assessed in mice and/or rats. Animals received different doses of citalopram [1, 2, 4, 8 or 16 mg/kg, i.p.] or its vehicle [saline] 30 min before training each day. The results showed no significant effects of citalopram on T-maze discrimination task in mice and rats. However, there was dose-dependent increases in latencies to find the invisible platform and traveled distances in citalopram received groups compared to the control group with the peak effect at doses of 4 and 8 mg/kg in Morris task. Therefore, it appears that citalopram can cause learning deficits in complex spatial tasks