The hippocampus and flexible spatial knowledge in rats

Lesions to the hippocampal system in rats result in a profound impairment of place or locale spatial learning although other learning strategies remain unaltered. The main objective of the present study was to investigate whether the spatial knowledge preserved in the hippocampal animals can be expressed flexibly under conditions different from those of the acquisition period. Rats with neurotoxic lesions to the dorsal hippocampus and sham-operated subjects were trained to reach the goal arm in a four-arm plus-shaped maze using a constant starting arm. During the training a transparent plexiglas barrier divided the maze in two equal halves in such a way that the animals could only travel from the starting arm to the goal arm, not having access to the remaining 50% of the maze. After seven days of training, a transfer test was used in which the starting arms were the two arms from which the animals had not started during the training phase. Results indicated that the lesioned rats made significantly more errors than the control subjects. But the most interesting results revealed that the kind of error made by the lesioned animals was congruent with the turn that they had to make during the acquisition phase in order to access the goal arm (reinforced). These results suggest that when the hippocampus is damaged a preserved highly inflexible egocentric strategy is employed to solve the spatial problem.     

Training history affects magnitude of spontaneous recovery from extinction of appetitive conditioned responding

Three experiments examined spontaneous recovery from extinction of appetitive conditioned responding (CR) as a function of training history. Rats first received reinforced and non-reinforced conditioning trials. Groups of rats were equated for total number of reinforced trials but differed in the number of non-reinforced trials, or in the order of reinforced and non-reinforced trials. CR was then extinguished in all groups. Subsequently, the extent of recovery of CR was assessed in a test session performed either 1 or 17 days after the last extinction session. After a 17-day delay, rats that had received all reinforced trials immediately prior to the first extinction session showed stronger recovery than did rats having received all reinforced trials at the beginning of training, or interspersed among non-reinforced trials. No significant spontaneous recovery was observed after a 1-day test delay. These results, which may be of clinical relevance with respect to relapse after therapy, are explained in terms of the training schedules generating differences in strength of inhibitory associations, and a relatively long, but not a short, test delay attenuating these associations.     

Effects of peripherally injected vasopressin and des-glycinamide vasopressin on the extinction of a spatial learning task in rats

An elevated eight-arm radial maze was employed to study the effects of neuropeptide administration on the spatial learning abilities of food-deprived rats. Following 18 days of reinforced training, each animal was briefly exposed to the maze with no food available in any of the eight food-cups. Immediately after this preliminary trial, animals were injected with a single subcutaneous dose of either saline, arginine vasopressin (AVP: 1.0 or 5.0 micrograms/kg), or an AVP analog with only weak endocrinological activity, des-gly-arginine vasopressin (DG-AVP: 1.0, 5.0 or 10.0 micrograms/kg). Additional extinction trials were conducted at 2, 4, 6 and 8 h post-injection. These tests consisted of individually placing an animal on the empty maze and recording the number of arms chosen in a 5-min period. In this situation, animals learn that food is no longer present in the maze and, consequently, extinguish responding. Vasopressin potentiated this radial maze extinction behavior while DG-AVP produced behavioral results directionally opposite to those predicted by a memory facilitation hypothesis. In a subsequent experiment, vasopressin had no effects on unconditioned locomotor activity measured 2 and 4 h post-injection. These results suggest that: vasopressin improved the learning that occurred during extinction of conditioned appetitive behaviors, these vasopressin effects on conditioned behavior were independent of any unconditioned, sedative or non-specific actions of the peptide, and peripheral endocrinological responses may be necessary to demonstrate memory-enhancing effects following peripherally administered AVP.     

Spontaneous light or dark preference in albino mice?

The present experiment examined spontaneous visual choice behaviour and acquisition of a positively reinforced visual discrimination task in Swiss albino mice. In experiment I animals were given 4 consecutive trials in which they could freely enter either a dimly illuminated or a darkened arm of a Y-maze; the position of the light stimulus was randomized across trials. D groups and L groups were tested during the dark and the light period of the day respectively. Results revealed a significant spontaneous preference for the illuminated arm of the maze, independent of the testing period. It is suggested that the dim light has a reinforcing value because it provides additional information about a novel environment. In a second experiment an appetitive visual discrimination task was carried out in the same Y-maze. After a pretraining period, half the animals were reinforced in the illuminated arm and half were reinforced in the darkened one, on five consecutive days. On the first test session all groups of animals chose the illuminated arm significantly more frequently, whereas light/dark choices reached chance level on the last test session. Discrimination learning was not acquired and a behavioural analysis revealed an increasing tendency to a side preference across testing.     

Modulation of long-term memory and extinction responses induced by growth hormone (GH) and growth hormone releasing hormone (GHRH) in rats

The purpose of this work is to study the participation of growth hormone (GH) and growth hormone releasing hormone (GHRH) in the modulation of long-term memory and the extinction response of a passive avoidance task in rats. However, the effect on memory vary according to the age of the animals due to plasma levels of either hormone being modified during the aging process. Male Wistar rats were divided according to age into two experimental blocks (young rats 3 months old and aged rats 24 months old at the start of the experiment) where each block received the same treatment. Each experimental block was then divided randomly into three groups where two were experimental and the other served as control. The animals were then submitted to a one-trial passive avoidance conditioning and tested for memory retention 24 hrs after as well as twice a week until the extinction response occurred. The control group received an isotonic saline solution and the other two groups received 0.8 U.I. Of GH or 4 mcg of GHRH respectively. All substances were in a 0.08 ml volume and applied 24 hrs before training as well as 24 hrs before each retention session. The results indicate that GH and GHRH modulate longterm memory as well as the extinction response and in either case the response seems to vary with age. GH and GHRH facilitates long-term memory in young rats but not in aged rats. Finally, whereas GH delays the extinction response in both groups, GHRH retards the extinction only in aged rats.     

Vasopressin retards the acquisition of positively reinforced lever pressing in homozygous Brattleboro rats

Previous studies have indicated that vasopressin treatment improves the poor performance of congenitally vasopressin deficient (Brattleboro) rats on shock avoidance paradigms, an effect thought to relate to the peptide's enhancement of mnemonic processing. In the present study, a food rewarded autoshaping task was used to study the acquisition, retention, extinction and subsequent re-acquisition of lever pressing. Vasopressin (1 μg/rat, subcutaneous) was found to impair acquisition in these animals.The possibility that this deleterious effect was due to a transient suppression of motor capability was tested in a second experiment. Vasopressin increased overall locomotor activity levels, but there was an indication that rates immediately following injection were lower than usual. An explanation for the effects of vasopressin based on arousal enhancement is discussed, and it is suggested that the neuropeptide may be concerned with the regulation of arousal and hence performance.     

Increased daily handling of ovariectomized rats enhances performance on a radial-maze task and obscures effects of estradiol replacement

Estrogen impacts performance on tasks of learning and memory, although there are inconsistencies in the direction and magnitude of the reported effects. Contributory factors to the inconsistencies may be methodological differences associated with different regimens of treatment. The goal of the present experiment was to assess the effect of increased handling, such as that commonly associated with pharmacological or other experimental manipulations, on the ability of estrogen to influence working memory performance. Young adult rats were ovariectomized and implanted with capsules containing either cholesterol or 25% estradiol diluted in cholesterol. Half of each hormone treatment group received standard handling, which consisted of handling required to carry out experimental procedures and half received increased handling, which consisted of standard handling as well as 2 min of additional daily handling by the experimenter. Animals were trained daily on a working memory task on an eight-arm radial maze for 24 days of acquisition and for eight additional daily trials in which delays of either 1 min or 3 h were imposed between the fourth and fifth arm choices. Animals that received increased handling exhibited significantly enhanced performance during acquisition and delay trials compared to those that received standard handling. Estradiol significantly enhanced performance during delay trials in animals that received standard handling but had no effect in animals that received increased handling. These results suggest that the amount of handling that animals receive as part of experimental procedures may obscure the memory enhancing effects of estradiol replacement on certain tasks of cognition.     

beta-Endorphin controls vasopressin release during foot shock-induced stress in the rat

This study tested the possibility that beta-endorphin is involved in the regulation of vasopressin release during stress induced by inescapable electric foot shock. To this end, a specific anti-beta-endorphin antiserum or a control serum lacking the specific anti-beta-endorphin antibodies was administered to male rats. Plasma vasopressin concentrations, measured by radioimmunoassay, were not affected by brief foot shock stress in control rats, but were raised significantly by the stress in animals which had received an intracerebroventricular (i.c.v.) injection of the anti-beta-endorphin antiserum. In contrast, when the same volume of the anti-beta-endorphin antiserum was injected into a tail vein, foot shock stress produced only a slight effect on vasopressin release. I.c.v. injection of the antiserum changed neither basal nociceptive threshold nor stress-induced analgesia as revealed by the tail-flick latency. Vasopressin release induced by an osmotic stimulus was not influenced by the anti-beta-endorphin antiserum given i.c.v. The opiate antagonist naloxone or the glucocorticoid dexamethasone raised plasma vasopressin concentration in stressed rats which had received the control serum (i.c.v.); however, after i.c.v. injection of the anti-beta-endorphin antiserum neither naloxone nor dexamethasone elevated the plasma vasopressin concentration beyond the level reached by the anti-beta-endorphin antiserum (i.c.v.) alone. These results suggest that beta-endorphin inhibits the release of vasopressin during foot shock-induced stress in the rat.     

Effects of lateral hypothalamic stimulation on acquisition,reversal and extinction of a visual discriminative learning task

The present experiment was carried out to investigate the effects of lateral hypothalamic (LH) stimulation on a negatively reinforced complex learning task including acquisition, reversal and extinction of a visual discrimination in an Y-maze. Male swiss mice were stimulated 45 sec after each training session during 60 sec (group ST). The stimulation intensity administrated in post-session was that which produced a rate of 50 responses by min during intracranial self-stimulation (ICSS) testing carried out prior to the learning experiment. Three control groups were constituted by animals either submitted to ICSS testing but not stimulated after training session (group NST). The post-session stimulated (group I) or non-implanted (group NI). The post-session stimulation improved the learning performance of the animals, but this effect was significant only during reversal learning of the task. ICSS testing carried out before learning, as well as electrode implantation, had no effect by themselves on the acquisition of the visual discrimination task. Moreover, no sign of extinction was observed in any group tested. These results suggest that facilitating effects induced by LH stimulation may depend on the complexity of the task and that cues of the learning situation have to reach a minimum of salience in order for LH stimulation to be effective.     

Age-dependent DOCA-salt hypertension in Brattleboro rats: the role of vasopressin

The age-dependent participation of endogenous vasopressin (VP) during the development of DOCA-salt hypertension was studied in young (28-day-old) and adult (75-day-old) Brattleboro rats. VP-deficient homozygous (DI) rats were compared to heterozygous (non-DI) littermates which do synthetize VP. Six weeks of DOCA-salt treatment did not increase blood pressure (BP) in adult DI rats. On the other hand, in young DI animals there was a significant rise of systolic and mean arterial pressure accompanied by the hypertrophy of the left ventricle. This moderate DOCA-salt hypertension of young DI rats contrasted with severe hypertension of young non-DI rats. Increased BP response of young VP-deficient DOCA-salt treated rats was independent of the saline intake or blood volume expansion which were similar in young hypertensive and adult normotensive DI animals. It could be concluded that vasopressin is not essential for the induction of DOCA-salt hypertension in young rats even if VP is responsible for the magnitude of BP elevation. In contrast to young animals vasopressin is very important for the development of DOCA-salt hypertension in adult rats.     

Rats more readily acquire a time-of-day go no-go discrimination than a time-of-day choice discrimination

Male Sprague-Dawley rats were used to compare six time-place training procedures that differed with respect to housing or training conditions. All procedures involved training food-deprived rats to enter one choice arm of a T-maze during a morning test session and to enter the other choice arm during an afternoon session to obtain Cocoa Puffs(R). The task proved to be difficult. Only 39 of 49 rats attained a criterion of nine correct choices on ten consecutive trials within a total of 120 trials. Making one choice arm distinct, limiting consecutive same correct choices to two, giving one session during the light and one during the dark portion of the light cycle, extinguishing perseveration of the same choice responses, and housing the rats with a natural light cycle all failed to significantly decrease the errors or trials to a 90% correct choice criterion. In contrast, all responding rats (n=7) showed significantly better than chance performance within 48 trials when the task was a go no-go discrimination based on time of day. Learning to make a response during a session when a choice to either choice arm is reinforced and to withhold responding during a session when a choice to neither choice arm is reinforced was relatively easy for the rats to acquire. Continued high level performance after the light cycle was eliminated, a random feeding schedule was initiated, and other time-related cues were masked suggests that the rats used internal cues or an internal clock to make the correct go or no-go response. It was concluded that rats are prepared to use time of day as an occasion-setting stimulus, but have difficulty using time of day as a signal for a specific response.     

Effect of neurohypophyseal peptides on the formation of a conditioned feeding reflex in the rat

The influence of intraperitoneal injection of vasopressin (LVP), oxytocin (OXY) and their fragments (DGAVP, PLG) on the acquisition and extinction of conditioned food reflex was studied in rats. It was found that vasopressin and its fragments had a more pronounced specific effect on the higher nervous activity of the animals. This effect consisted in impairment of the performance of the conditioned food reflex while oxytocin had a tendency to improve its performance. On the ground of the obtained data it is suggested that administration of vasopressin may facilitate the memory function only under specific environmental conditions.     

Effect of desglycinamide-lysine vasopressin (DG-LVP) on sexually motivated T-maze behavior of the male rat

Desglycinamide lysine vasopressin (DG-LVP), a vasopressin analog which has been found to facilitate the maintenance of active and passive avoidance behavior, influences the retention of a sexually motivated choice behavior of male rats in a T maze. A higher percentage of rats receiving DG-LVP after each acquisition session shows a correct choice during free-choice retention trials. The total number of correct choices is also higher than in the controls. Copulation reward after a correct choice is an essential requisite for acquiring the choice response and retention effect of DG-LVP. Male rats which were prevented from copulating with the receptive female goal rat or which were presented with another male in the goal box did not acquire the response, and their behavior was not influenced by DG-LVP. Response latencies were never affected by the peptide. It is concluded that the long-term effect of vasopressin on learned behavior is of a rather general nature and is most probably due to facilitated memory consolidation processes.     

Intertrial interval as a contextual stimulus

Four experiments with rats investigated whether the time between appetitive conditioning trials can serve as a discriminative cue for responding during the next conditional stimulus (CS). In Experiment 1, rats that received extinction trials with a 4-min intertrial interval (ITI) showed spontaneous recovery after a retention interval of 16 min, whereas rats that received extinction with a 16-min ITI did not. Experiments 2 and 3 investigated more explicit discriminations between the 4- and 16-min ITIs. When a 16-min ITI signaled that the CS would be reinforced and a 4-min ITI signaled that it would not, the ITIs modulated responding to the CS. But when the 4-min ITI signaled reinforcement and the 16-min ITI did not, there was less evidence of modulation by the ITIs. This asymmetry was due at least partly to a difficulty in performance rather than learning. Experiment 4 investigated similar discriminations with 1- and 4-min ITIs. Here the results took a different form: time in the reinforced ITI elicited responding directly, but did not modulate responding to the CS. ITI can function as a contextual cue, and the results suggest new similarities between the processes behind interval timing and associative learning.     

奖励性操作式条件反射任务在大鼠学习记忆研究中的应用

目的将奖励性操作式条件反射方法应用于学习记忆研究。方法首次采用奖励性操作式条件反射方法,设置单次操作训练、连续多次操作训练、信号辨识与消退四种检测模式,研究Wistar大鼠和SHR大鼠学习记忆能力。结果奖赏训练中,SHR组鼻触次数显著增多（vs.Wistar＆Donepezil,P〈0.05）;单次操作训练中,三组动物对操作反应的获得无显著差异;连续多次操作学习任务中,SHR组错误操作次数增多（vs.Wistar,P〈0.05）,奖赏获得次数减少（vs.Donepezil,P〈0.001）,反应准确率显著降低（vs.Wistar＆Donepezil,P〈0.05）;信号辨识任务中SHR组错误反应次数显著增多（vs.Wistar＆Donepezil,P〈0.05）,而反应准确率降低,组间差异有显著性（vs.Wistar＆Donepezil,P〈0.05）;消退实验中,三组动物差异无显著性。神经递质检测发现,SHR组大鼠谷氨酸[（1.0639±0.07086）mg/g]、乙酰胆碱[（2.7760±0.2609）μg/g]与五羟色胺[（1.2200±0.1137）μg/g]含量均显著低于Wistar组大鼠（P〈0.05）,多奈哌齐组大鼠乙酰胆碱含量显著增加[（3.9344±0.2747）μg/g]（vs.Wistar,P〈0.05;vs.SHR,P〈0.001）。结论奖励性操作式条件反射方法可作为一种正性增强条件反射检测新方法应用于大鼠学习记忆研究。     

Chronic corticosterone treatment enhances extinction-induced depression in aged rats

Withdrawal and avoidance behavior are common symptoms of depression and can appear as a consequence of absence of reward, i.e. extinction-induced depression (EID). This is particularly relevant for the aged organism subjected to pronounced loss of former rewards. Avoidance of the former site of reward and increased withdrawal into a distant compartment accompany extinction of food-rewarded behavior in rodent models. During extinction, behavioral markers for re-learning dissociate from indicators of extinction-induced depression. Here we examined the effect of a chronic treatment with corticosterone (CORT), a well-known inducer of depression-related behavior, on EID in adult and aged rats. Adult (3–4 months) and aged (18 months) male rats were treated with CORT via drinking water for 3 weeks prior to extinction of a cued food-reward task. CORT treatment increased the distance from the site of reward and decreased goal tracking behavior during extinction, especially in the aged rats. Plasma hormone levels measured before and after restraint stress showed a decline in basal ACTH- and CORT-levels after chronic CORT treatment in aged animals. The treatment significantly impaired the HPA-axis activation after acute stress in both, adult and aged animals, alike. Altogether, these findings show an enhancement of EID after chronic CORT treatment in the aged organism, which may be mediated by an impaired HPA-axis sensitivity. These findings may have special relevance for the investigation of human geriatric depression.     

大鼠眶额叶皮质受损破坏新异性探索行为

利用旷场测试和Y-迷宫测试两种行为模型检测了双侧眶额叶（orbitofrontal cortex, OFC）电损伤或假损伤雄性SD大鼠的新异性探索行为, 探讨了OFC在大鼠探索新异环境中的作用。旷场测试的结果发现,OFC损伤大鼠的行走距离和直立次数较假损组有明显降低;同时,在Y-迷宫测试中与假损伤组大鼠相比,OFC损伤大鼠在新异臂的访问时间和穿梭次数明显降低。提示眶额叶皮质在大鼠新异性探索行为中起着重要作用。     

The role of contextual conditioning in the effect of reinforcer devaluation on instrumental performance by rats

Different groups of rats received different amounts of training to lever press for a food reinforcer before an aversion was conditioned to the food. This devaluation of the reinforcer reduced responding in both subsequent extinction and reinforced tests of responding to a degree that was independent of the amount of instrumental training. Moreover, interpolating context extinction between aversion conditioning and the extinction test reduced the magnitude of the devaluation effect, thereby indicating that Pavlovian contextual conditioning may play a role in the instrumental devaluation effect.     

Hyperreflexive behavior in Brattleboro rats

In two experiments we compared the size of the startle response elicited by shock and acoustic stimuli in animals having a congenital absence of vasopressin (Brattleboro rats) with closely related controls, which do synthesize vasopressin. The rats lacking vasopressin were hyperresponsive to both shock and acoustic stimuli. Inhibition of the acoustic startle by shock prestimuli also was greater in these animals. These results are consistent with reports which indicate that vasopressin attenuates responses to noxious stimuli.     

Central cardiovascular effects of mammalian neurohypophyseal peptides in conscious rats

To confirm and extend the results of previous studies which demonstrated central cardiovascular effects of vasopressin in anesthetized rats, we determined blood pressure and heart rate changes for 30 minutes after intracerebroventricular injections of arginine vasopressin, arginine vasotocin and oxytocin in conscious rats. As compared to sham injections, significantly greater increases in either systolic or diastolic blood pressure were noted over the 30 minutes which followed the injection of 0.15, 1.0 or 10.0 nM of either vasopressin or vasotocin. In animals given vasopressin, plasma levels of the peptide were determined. There was a substantial increase in plasma vasopressin only after the highest dose. Overall blood pressure responses to doses of oxytocin as high as 100 nM were not significantly different than sham injections. Heart rate following both vasopressin and vasotocin was increased at 0.15 nM, was initially decreased then increased at 1.0 nM and was substantially decreased after the 10.0 nM dose. There was a significant increase in heart rate at the 10.0 nM and 100 nM doses of oxytocin. Dose response curves for systolic blood pressure and heart rate 20 minutes after injection were similar for vasopressin and vasotocin. We conclude that arginine vasopressin has significant central pressor and tachycardic effects in conscious rats, and it is related, at least in part, to the tail structure of the peptide, which is shared with arginine vasotocin.