Effects of green tea extract on learning, memory, behavior and acetylcholinesterase activity in young and old male rats

Objective

To study the effects of green tea extract administration on age-related cognition in young and old male Wistar rats.

Methods

Young and old rats were orally administered 0.5% green tea extract for a period of eight weeks and were evaluated by passive avoidance, elevated maze plus paradigm and changes in acetylcholinesterase activity.

Results

Treatment of young and old rats with the extract resulted in no significant difference in performance on the rota rod treadmill test/righting reflex time. Green tea extract significantly improved learning and memory in older rats, with increased retention latency to enter difference in passive avoidance test. In the elevated maze test, green tea treatment resulted in significantly more number of entries in the enclosed arm by the young and old rats. Decline in acetylcholinesterase activity was observed in the cerebrum of green tea treated old rats in comparison to the green tea treated young rats.

Conclusion

Green tea extract administration is effective in enhancing learning and memory in aged rats, and hence, may serve useful in reversing age-related deficits.     

Locomotor, avoidance,and maze behavior in rats with selective disruption of hippocampal output.

Behavioral correlates of selective disruption of hippocampal output were investigated in a series of five experiments. In two experiments an attempt was made through behavioral investigation to determine whether the CA1 neurons project to the fimbria or to the subiculum. The results supported recent views that the subiculum is the recipient of CA1 axons. Disruption of the CA1 output in the dorsal hippocampus of rats produced increased open-field activity, whereas passive avoidance and spontaneous alternation behaviors remained unchanged. No differentiation was obtained between CA1 damage and neocortical lesions in maze learning. Blocking of the fimbrial CA3 output from the dorsal hippocampus improved passive avoidance performance and impaired active avoidance performance, whereas open-field and spontaneous alternation behaviors were unaffected. Interruption of the CA3 output from the ventral hippocampus improved active avoidance performance and reduced spontaneous alternation behavior. Open-field behavior and passive avoidance performance remained unchanged. Total fimbrial sections increased open-field activity, improved passive and active avoidance, and reduced spontaneous alternation. The results are discussed in terms of functional differentiation between the CA1 and CA3 of the dorsal hippocampus and in terms of functional differences in the fimbrial CA3 output from the dorsal and ventral hippocampus.     

Deficient passive and one-way active avoidance acquisition following medial forebrain bundle lesions in rats.

Cathodal electrolytic lesions of the medial forebrain bundle (MFB) at posterior hypothalamic levels in male hooded rats produced a mild, transient hypodipsia and lowered jump thresholds to footshock. The lesions produced marked deficits in passive avoidance performance in a paradigm that paired discrete, linearly incrementing footshock intensities with contact of a water spout following 48 hr of water deprivation. Intraperitoneal injections of DL-5-hydroxytryptophan (75 mg/kg), the immediate metabolic precursor of serotonin, had no effect on the passive avoidance performance of either experimental or operated control subjects. Lesions of the MFB also resulted in deficient acquisition in a one-trial step-through passive avoidance paradigm not using motivation to drink and caused a severe acquisition deficit in a one-way active avoidance task. Lesions of the septal nuclei produced lowered jump thresholds but did not affect acquisition in the first passive avoidance task. The results are interpreted as indicating a lesion-induced deficiency in fear learning, independent of the serotonergic functions of the MFB.     

Calcium channel antagonists enhance retention of passive avoidance and maze learning in mice

Although a number of studies have shown that treatment with calcium channel antagonists (CCAs) can ameliorate impairments in learning and memory in aged animals, evidence for a general nootropic effect of CCAs in neurologically normal young adult animals is ambiguous. This study attempts to resolve some of this ambiguity by comparing the effects of several CCAs on retention of passive avoidance learning and acquisition and retention of appetitively motivated spatial discrimination learning in young adult mice. Animals were trained in a step through passive avoidance apparatus and, immediately after training, injected subcutaneously with different doses of nimodipine, nifedipine, amlodipine, flunarazine, diltiazem, or verapamil. Retention was tested 24 h after training. In the maze-learning task mice were treated with the same doses of the aforementioned CCAs immediately after a brief training session in a linear maze and retention was tested 24 h after training. The most effective dose of each agent in the maze-retention experiment was administered to additional groups of animals 1 h prior to training to determine the effects of CCAs on acquisition processes. The effects of central administration of CCAs were examined by intracerebroventricular injection of different doses of amlodipine immediately after passive avoidance training. Results showed (1) all peripherally administered drugs except verapamil facilitated retention of passive avoidance training in a dose-dependent manner, (2) all drugs dose dependently facilitated retention of linear maze learning, (3) all doses of the drugs (except verapamil) which facilitated maze retention also facilitated maze learning, and (4) central administration of the dihydropyridine amlodipine produced a dose-dependent facilitation of the retention of passive avoidance learning. These data indicate that drugs which block calcium channels can enhance retention of two different types of learning in mice.     

Effects of losing and testosterone upon subsequent behavior in male and female S3 (Tryon Maze Dull) rats

Attempts were made to determine whether modification of agonistic behavior by experience differs in the sexes and if so, whether testosterone is involved in this response. Gonadectomized male and female CPB-S3 (Tryon Maze Dull) rats were treated with testosterone propionate (TP, 250 μg) or vehicle and subjected to tests in which they became either winners or losers. S3 males and females were tested against Long Evans rats to become losers or against Wistar rats to become winners. Subsequently, S3 winners were tested against losers. In addition, winners and losers were tested against naive S3 opponents of the same sex. After varied agonistic experiences, all animals were tested for social preference in a situation in which they could choose between their respective opponents without the possibility of social interaction. Thereafter, they were also exposed to a two-choice passive avoidance learning procedure to see if the behavioral effects of aggressive interactions generalized to nonsocial learning. Males and females reacted differently to winning or losing, the presence of testosterone being a critical factor in the manifestation of this sex difference. Relatively permanent effects on aggressive and other behaviors were only established in TP-treated males. Losing experiences in the social-preference test generally led to a slight preference for naive, less aggressive animals. Testosterone-treated male losers, the group expected to be most vulnerable to generalized inhibition and impairment of learning, did not differ from other categories in the two-choice passive avoidance procedure, although marked differences were observed between the sexes and between testosterone and oil-treated animals.     

Stimulus selection in passive avoidance learning and retention: weanling, periadolescent, and young adult rats

Periadolescent rats exhibit a number of behavioral differences in comparison with younger or older animals. For instance, periadolescents tend to show enhanced acquisition of simple active avoidance tasks, but impaired acquisition of more complex appetitive and aversive discriminations. In this experiment, rats were trained on a simple passive avoidance task at one of three ages, as weanlings (25 days), periadolescents (35 days), or young adults (45 days). Training occurred in the presence of both a redundant discriminative stimulus and a specified, redundant contextual stimulus. The periadolescents did not differ from either younger or older rats in rate of learning the passive avoidance task. The retention performance of these animals was then tested following a change in either, neither, or both of the redundant cues. When a measure of performance that controls for baseline activity was used, it was observed that periadolescents were not disrupted by a change in the redundant discriminative stimulus, a cue change that clearly disrupted performance in 25- and 45-day-old animals, and tended to be more disrupted by the contextual change than younger or older rats. It is hypothesized that the alterations in performance exhibited by periadolescents may be related to an ontogenetic alteration in stimulus selection modulated by the catecholaminergic systems.     

The Reinforcing Effect of a Differentiating Stimulus

Twenty Sprague Dawley rats, aged 22 to 26 months were given subcutaneous injections of 4.5 mg/kg methylphenidate or distilled water. Twelve minutes after the single injection was given, rats began 90 trials of avoidance conditioning. Drug animals made significantly more correct responses than did the control animals. Results indicate that use of methylphenidate in aged rats improved avoidance learning.     

Intrahippocampal insulin improves memory in a passive-avoidance task in male wistar rats

The main impacts of insulin favor the peripheral organs. Although it functions as a neuropeptide, insulin possesses also some central effects. The aim of this study was to determine the effect of intrahippocampal infusion of insulin on passive avoidance learning in healthy male rats. Thirty male wistar rats were divided into three groups (n=10 each). The experimental group had posttraining insulin infusion into the CA1 region of dorsal hippocampus, after which they were compared with sham (saline) and control (intact) groups. Insulin treated animals had greater latency to enter the dark compartment in compare with saline treated (p=0.023) or control groups (p=0.017). Upon our results, we concluded that intrahippocampal injections of insulin may enhance memory for a simple learning task which supports the concept that insulin possibly plays an endogenous role in memory formation.     

Running-wheel avoidance learning in rats (Rattus norvegicus): effects of contingencies and comparisons of different strains

In Experiment 1, we showed that active- and passive-avoidance responding in a running wheel was learned because of the avoidance contingency. In Experiment 2, strain differences among four commercially bred rats were assessed in an active-avoidance paradigm. Wistar, Donryu, and Fischer rats learned faster than Sprague-Dawleys. In Experiment 3, learning in a multiple active/passive avoidance schedule was examined, and both components of this task were learned. This multiple schedule was used to investigate strain differences in selectively bred rats in Experiments 4 and 5. Tsukuba low-emotional (TLE) rats responded more than Tsukuba high-emotional (THE) rats in both components. However, discrimination of passive components was better in THE than in TLE rats. Syracuse high-avoidance rats were superior in the active component, whereas Syracuse low-avoidance rats showed superior performance in the passive component.     

Assessment of retention capacities in old rats

Young (3-6 month) and old (24-27 month) barrier reared Wistar rats were tested for their ability to retain an inhibitory (passive) avoidance, acquired immobility, and a conditioned taste aversion response as a function of time. Old rats exhibited accelerated forgetting of both the inhibitory avoidance and acquired immobility response in comparison to young rats. In contrast, old rats displayed good retention of the conditioned taste aversion response at all time intervals tested. It appears that the dynamic aspects of retention are altered in aged rats depending on the task, and in some instances may be expressed as accelerated forgetting.     

Lesions of the intermediate medial hyperstriatum ventrale impair sickness-conditioned learning in day-old chicks.

Lesion studies show that the intermediate medial hyperstriatum ventrale (IMHV), a forebrain visual association area in chicks, is involved in learning and memory for one-trial passive avoidance and imprinting. We examined the effects of IMHV lesions in a one-trial, nongustatory, sickness-conditioned learning task. This task is similar to passive avoidance and imprinting because all three tasks require the chick to remember visual cues in order to respond correctly. However, sickness-conditioned learning differs from imprinting and passive avoidance because it uses sickness as the aversive stimulus and there is a longer conditioned stimulus-unconditioned stimulus interval (30-min delay compared to seconds). Bilateral IMHV lesions given 24 h before training impaired the ability of the chicks to avoid a bead associated with sickness produced by lithium chloride injection, as did pretraining unilateral left or right IMHV lesions. Post-training IMHV lesions given 1 h after training did not impair avoidance of the test bead in the sickness-conditioned learning task. However, lesioned chicks showed generalized avoidance of all test beads. The pretraining lesion results are similar to those found in imprinting and passive avoidance learning; however, the effects of unilateral IMHV lesions differed. Post-training lesion effects are similar to those found in passive avoidance learning. We propose that both left and right IMHV are necessary for sickness-conditioned learning and that post-training IMHV lesions impair the ability of the chick to learn or remember the association between the color of the bead and the aversive consequences of LiCl injection.     

Limbic networks and associative learning: II. Entorhinal contributions to spontaneous alternation, passive avoidance, and taste aversion learning

The hippocampus plays an important role in learning and memory, but the precise nature of that involvement remains uncertain. Transection of the perforant path, a primary input pathway to the hippocampus, has been shown to produce changes in reaction to novelty and acquisition of active avoidance; the nature and magnitude of these changes vary with lateral or medial perforant path damage. In a series of experiments on adult rats, the role of these pathways in spontaneous alternation, exploration, acquisition and extinction of conditioned responses, passive avoidance, and conditioned taste aversion was investigated. Lateral transection reduced exploration while medial transection facilitated acquisition of an active avoidance response; no effects were observed on any other measure. Results are discussed in terms of what perforant path damage might reveal regarding the interactions of the hippocampus with other brain regions.     

Limbic networks and associative learning: II. Entorhinal contributions to spontaneous alternation,passive avoidance,and taste aversion learning

The hippocampus plays an important role in learning and memory, but the precise nature of that involvement remains uncertain. Transection of the perforant path, a primary input pathway to the hippocampus, has been shown to produce changes in reaction to novelty and acquisition of active avoidance; the nature and magnitude of these changes vary with lateral or medial perforant path damage. In a series of experiments on adult rats, the role of these pathways in spontaneous alternation, exploration, acquisition and extinction of conditioned responses, passive avoidance, and conditioned taste aversion was investigated. Lateral transection reduced exploration while medial transection facilitated acquisition of an active avoidance response; no effects were observed on any other measure. Results are discussed in terms of what perforant path damage might reveal regarding the interactions of the hippocampus with other brain regions.     

Long-term consequences of early experience on adult avoidance learning in female rats: role of the dopaminergic system

Following our hypothesis that juvenile emotional and/or cognitive experience should affect learning performance at preweaning age as well as adulthood, the present study in female Wistar rats aimed to examine the impact of (i) avoidance training at preweaning age, (ii) exposure to repeated maternal separation, (iii) the combination of both, and (iv) the blockade of dopaminergic neurotransmission on adult two-way active avoidance learning in rats. We found that preweaning, i.e. three week old, rats were less capable of avoidance learning compared to adults. Our main findings revealed that preweaning avoidance training alone improved avoidance learning in adulthood. Furthermore, maternal separation alone also improved avoidance learning in preweaning and in adult rats, but this effect of maternal separation did not add up to the beneficial effect of preweaning avoidance training on adult learning. In addition, the pharmacological blockade of dopamine receptors during preweaning avoidance training via systemic application of haloperidol impaired preweaning avoidance performance in a dose-dependent manner. Testing the haloperidol-treated preweaning presumed "non-learners" as adults revealed that they still showed improved learning as adults. Taken together, our results strongly support the hypothesis that emotional as well as cognitive experience at preweaning age leaves an enduring "memory trace," which can facilitate learning in adulthood. Our pharmaco-behavioral studies suggest that unlike the adult brain, preweaning learning and memory formation is less dependent on dopaminergic mechanisms, which raises the intriguing question of possible alternative pathways.     

Intracerebroventricular effects of angiotensin II on a step-through passive avoidance task in rats

A wealth of evidence indicates that angiotensin II (Ang II) is involved in learning and memory. However, the precise role of this peptide in these cognitive processes is still controversial, with data indicating either an inhibitory or an enhancing action. The present study was designed to further investigate the effects of intracerebroventricular injections of Ang II (0.5, 1 or 3nmol/5microl) on a step-through passive avoidance task in male adult Wistar rats. When administered pretraining, Ang II did not affect the acquisition of passive avoidance, but markedly improved avoidance performance when given before the retrieval test. The latter effect was observed in retest sessions performed up to 72h after training. Administration of the peptide five minutes after training impaired retention of inhibitory avoidance. Therefore, Ang II may exert opposite effects on passive avoidance memory according to its interference with brain mechanisms leading to the storage or retrieval of this aversively motivated task.     

Reaction to punishment, reflectivity, and passive avoidance learning in extraverts

Passive avoidance learning occupies a central role in accounts of disinhibited behavior, ranging from psychopaths' persistent criminality (Hare 1970) to extraverts' gregariousness (Gray, 1972). To explore the mechanism underlying passive avoidance deficits, we assessed the relation of extraversion, neuroticism, and response latency after punishment to passive avoidance learning by using two successive go/no go discrimination tasks. The tasks were designed to examine two aspects of subjects' reactions to punishment: response speed on trials immediately following punishment (Experiment 1) and time to terminate punishment feedback between successive trials (i.e., reflectivity; Experiment 2). Consistent with previous findings, the results of Experiment 1 showed that extraverts commit more passive avoidance errors than introverts do (Newman, Widom, & Nathan, 1985) and fail to pause following punished errors (Nichols & Newman, 1986). In Experiment 2, only neurotic extraverts displayed this pattern of performance differences. In both experiments, longer pausing following punishment predicted better learning from punishment for both introverts and extraverts. These results suggest that, in the presence of salient cues for reward, extraverts' characteristic reaction to punishment interferes with processing punished errors and may contribute to their more general propensity for impulsive, nonreflective action.     

Chronic amphetamine exposure during the preweanling period does not affect avoidance learning or novelty-seeking of adult rats

The purpose of the present study was to determine whether exposure to amphetamine during the preweanling period would impact the learning or reward processes of rats tested in adulthood. In three experiments we examined whether amphetamine treatment (0-10 mg/kg per day) on postnatal days 11-17 altered the subsequent performance of adult Sprague-Dawley rats on a step-down passive avoidance, active avoidance, or novelty-seeking task. There was no evidence that postnatal amphetamine exposure affected performance on any of these tasks. These results suggest that the long-term impact of pre- and postnatal psychostimulant exposure differs, because in utero stimulant treatment is known to produce learning deficits and decrease reinforcement efficacy of rats tested in adulthood.     

Postacquisition injection of tetrodotoxin into the parabrachial nuclei elicits partial disruption of passive avoidance reaction in rats.

The recent discovery that post-trial functional blockade of the parabrachial nuclei by intracerebral injection of 10 ng tetrodotoxin (TTX) disrupts acquisition of conditioned taste aversion (CTA) (Ivanova & Bures, 1990a,b) has prompted attempts to ascertain the role of this structure in other types of inhibitory learning. In Experiment 1, rats with implanted parabrachial cannulae were trained in a step-through avoidance task and received bilateral TTX (2 x 10 ng) immediately after the acquisition trial; they displayed significantly weakened avoidance of the shock compartment 2 days later. In Experiment 2, rats were anesthetized with pentobarbital (50 mg/kg) immediately after passive avoidance acquisition and received parabrachial TTX 15 min later; whereas anesthesia alone left the passive avoidance reaction (PAR) unaffected, TTX elicited similar disruption as in unanesthetized animals. In Experiment 3, TTX was injected in anesthetized animals 0, 1, 2, or 4 days after PAR acquisition. The amnesic effect was significant when the acquisition-TTX delay had been prolonged to 24 but not to 48 or 96 h. Since CTA is disrupted by reversible blockade of parabrachial nuclei and of the adjacent reticular formation elicited up to 4 days after acquisition (Ivanova & Bures, 1990b), PAR seems to be impaired to a lesser degree and for a shorter time than CTA by similar TTX treatment.     

The effects of control and lack of control on active and passive avoidance in rhesus monkeys

Most studies which have examined the effects of lack of control have utilized test tasks in which active responding is required, and generally they have found impaired learning. Those few studies which have required passive responding in the test task generally have found facilitation of learning. The present two experiments examined the effects of lack of control in both active and passive avoidance tasks in a primate species (Macaco mulatta) not previously used in this research area. In Experiment 1, although the group without control (IE) tended to be inferior at active and superior at passive avoidance in comparison to the group with control (E), there were no significant differences. In Experiment 2, utilizing a difficult discrimination task in which subjects were required to learn when and when not to respond actively to avoid aversive stimulation, greater group differences were found. Two monkeys from Group IE failed to escape in active avoidance acquisition and, as a whole. Group IE was somewhat slower to respond than Group E. At passive avoidance, however. Group IE was superior to Group E and, as a consequence, more efficiently solved the discrimination problem. Implications of the present results for interpretation of the effects of lack of control as deficits are discussed.     

Genetic differences in avoidance learning by Rattus norvegicus: escape/avoidance responding, sensitivity to electric shock, discrimination learning, and open-field behavior

The behaviors of rats selectively bred for either good or poor shuttle box avoidance learning were studied. The results of Experiment 1 indicated that the phenotypic difference in avoidance learning is not associated with differences in speed of escape or avoidance responding. Differences between the lines in frequency of intertrial responses (ITRs), which appear during training but not during pretest, suggest that ITRs in animals of the low-avoidance (SLA) line are more suppressed by electric shock than in animals of the high-avoidance (SHA) line. This result suggests that SLA animals may be more emotionally responsive than SHA animals. Experiment 2 demonstrated that the animals of the two lines do not differ in absolute sensitivity to electric shock, and Experiment 3 showed that the poor performance of the SLA line is not due to an inability to learn. Experiment 3 also provided evidence which suggests that the poor avoidance learning by SLA animals is due to their emotional reactivity. Observations of open-field behavior in Experiment 4 are consistent with this hypothesis. The major consistent correlate of the phenotypic difference in avoidance learning is greater emotionality or emotional reactivity in SLA than in SHA animals.