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PubMed1992

Effect of administration of an analog of LHRH on appetitive learning in young and middle-aged female rats.

Hypothalamic luteinizing hormone-releasing hormone (LH-RH) had been reported to induce changes in defensive learning. In middle age, females exhibit a decline in their reproductive axis. Several studies in rodents suggested that hypothalamic LHRH function deteriorated in middle-aged females. Our experiments compare T-maze learning in young and middle-aged female rats and study the effect of administration of an analog of LHRH, D-Trp6-LHRH. The ovarian action of the analog was studied and a gonadectomized control group was added. No differences were observed between young and middle-aged females in acquisition, retention, and reversal of a simple discrimination in the T-maze. However, after removal of motor and spatial cues acquisition of the discrimination on visual cues was impaired in middle-aged females compared to young mature ones. Administration of D-Trp6-LHRH enhanced performance during the visual discrimination in younger females and had no action in middle-aged ones, whereas it inhibited ovary function in both groups. Ovariectomy had no effect. These results suggest a direct effect of the analog of LHRH on the CNS and show that this peptide fails to counteract the deleterious effect of age on performance.

Aging↗
PubMed1981

The effect of intrahypothalamic serotonin reinforcement on directional preference in rats.

Reinforcing properties of serotonin administration to the lateral hypothalamus were tested on the experimental model of the T-maze learning in 19 rats. The results did not definitely prove either positive or negative reinforcement produced by the central serotonergic stimulation, although the rats modified their behavior in the maze in the response to intrahypothalamic serotonin. It seems that the central serotonergic neurons do not play a decisive role in the mediation of the reinforcing phenomena but they may interact with the activity of some other reward neurons.

Animals↗
PubMed1992

Smoking deprivation in "early" and "late" smokers and memory functions.

Reports on smoking and nicotine effects upon memory are contradictory: improvement, no change, and impairment have been observed. These inconsistencies may be due at least in part to different types of learning tasks and to experimental designs: in most studies, acute nicotine effects were analysed after previous smoking deprivation. This study compared learning, retention, and retrieval between nonsmoking after previous deprivation and "usual" smoking without previous deprivation. Twenty female smokers (S) participated in two sessions, between 8.00 and 11.00 a.m. The Austin maze and a Word Recognition Task (WRT) were applied. During the WRT, ERP were recorded from Fz and Cz scalp locations. Heart rate, CO, and subjective ratings (dizziness and smoking need) but neither WRT nor maze performance discriminated between deprivation and smoking. However, significant differences were obtained between those Ss who usually start smoking within 1 h after getting up (ES) and those who start later (LS). In maze learning and WRT, LS performed better when deprived than smoking, and ES performed better when smoking than deprived, i.e. when the time of the tests met their usual smoking habits. Results are discussed in terms of a modulation of smoking effects on memory functions by the Ss' internal state.

Adult↗
PubMed1997

Hippocampal degeneration inducing impairment of learning in rats: model of dementia?

In the pharmacological field, the development of drugs effective for dementia is now widely anticipated because of the increase in the elderly population. Dementia has some histological degeneration in the brain, including the hippocampus. Preclinical evaluations of such drugs use animal models with memory impairment, since memory impairment is a major criterion of dementia. We therefore investigated two animal models with hippocampal degeneration. Neonatal administration of monosodium glutamate (MSG) induced specific degeneration of hippocampal pyramidal cells in the CA1 region of Wistar rats in adulthood. In these animals, the correct response rate during the acquisition period of light-dark discrimination learning was significantly lower than that in the control group. No significant changes were noted in the hippocampal concentrations of neurotransmitter substances, including acetylcholine and glutamate. In the second model, similar histological changes were observed at 3 weeks after oral administration of trimethyltin (TMT). These histological changes were accompanied by a reduction in the intrahippocampal concentrations of acetylcholine and glutamate. In the case of light-dark discrimination learning, neither pre- nor post-training administration of TMT affected the correct response rate during both the acquisition and retention test periods. In the case of 8-arm radial maze learning, the increase in correct response rate was significantly suppressed in comparison with that of the control group when TMT was administered at 4 weeks before starting the acquisition trial. This suppression was followed by a lower response rate in the retention test. On the other hand, the correct response rates in retention tests were not affected when TMT was administered after completion of the acquisition trial. These findings indicate that sole degeneration of the hippocampus was able to induce different types of memory impairment, and single evaluation of a drug with one learning paradigm was difficult to justify that a drug is effective for dementia.

Animals↗
PubMed1989

Region selective increase in activities of CNS cholinergic marker enzymes during learning of memory tasks in aged rats.

The effects of learning memory tasks on activities of choline acetyltransferase (ChAT) and acetylcholinesterase (AChE) in the frontal cortex (FC), hippocampus (HC) and cerebellum of aged rat brains were studied in comparison with those of young adult rats. Aged rats were significantly inferior than young adult rats in both active avoidance (two-way shuttle box) and water-filled multiple T-maze learning. ChAT activity in the FC of aged rats was significantly increased after 5 days of training in an active-avoidance learning task. ChAT activity in the HC of aged rats was also significantly increased after 6 days of training in a water-filled multiple T-maze. These changes did not occur in young adult rats after either 2 or 5 days of active avoidance training, or in aged rats after 10 days of training, both of which were after the maximum level of learning of active avoidance task had been attained. AChE activity was significantly lower in the FC and HC of nontrained aged rats when compared with that of nontrained young adult rats. The reduced activity of AChE in both brain regions of nontrained aged rats rose to almost the same level as that in young adult rats in nontrained and trained states in an active avoidance task. From these findings, it is hypothesized that the task-dependent elevation in the activities of the central nervous system (CNS) cholinergic marker enzymes in trained aged rats may be compensatory changes to keep a relevant level of neurotransmission in the face of specific motor and/or cognitive insults.

Acetylcholinesterase↗
PubMed1986

Feeding neophobia: a possible explanation for the differential maze performance of rats reared in enriched or isolated environments.

This study undertook a detailed examination of the now-classical isolate maze deficit. Three male littermates from each of 19 litters were exposed to early and lengthy environmental enrichment, isolation, or isolation plus frequent handling. At 120 days of age subjects were tested on the open field, on an emergence task, and in a complex maze. Subjects were allowed to enter and leave the maze goal box at will. Only after eating for 30 seconds were they captured and replaced in the start box for the next trial. In the open field and emergence tasks the enriched and isolate rats both showed symptoms of much greater timidity than the experimenter-adapted handled rats. In the maze, enriched rats increased goal box entries over days, handled and non-handled isolates did not. By day three, handled and non-handled isolate goal entries were significantly lower than for enriched rats. This finding suggests an intellectual deficit in isolate maze learning. However, error analysis revealed that even on day one, all groups made errors at a rate far below random. The pattern of errors implied that subjects were often actively avoiding the goal, with isolates turning aside before entering the goal significantly more often than enriched rats. These findings suggest that the isolate maze deficit is due to a form of feeding neophobia. More generally, it would appear that these behavioral differences reflect early learning, with handled rats less afraid of humans and enriched rats better adapted to eating in novel surroundings.

Animals↗
PubMed2006

Effects of Ginkgo biloba administered after spatial learning on water maze and radial arm maze performance in young adult rats.

Ginkgo biloba is reported to improve learning and memory in animals. However, many studies do not directly test the effects of Ginkgo on memory because the drug is administered during the learning phase of the experiments. In this study, we examined the effect of 10 mg/kg, 20 mg/kg, or 40 mg/kg G. biloba extract on spatial memory by administering the drug in the interval between training and testing. Rats were tested for long-term reference memory retention in the radial arm maze and in the Morris water maze during daily probe trials in which the hidden platform was removed. G. biloba had no effect on reference memory in either the water maze or radial arm maze. To test short-term working spatial memory using the radial arm maze, animals were removed after receiving the reward from 4 of the 8 arms and were returned to complete the maze 2 h later. While Ginkgo had no effect on working memory, over time animals exposed to Ginkgo learned task better than control animals. Thus, Ginkgo appears to enhance neither short-term working memory nor long-term reference memory, but it may promote learning of spatial information.

Animals↗
PubMed1990

Sex differences in spatial ability and activity in two vole species (Microtus ochrogaster and M. pennsylvanicus).

The hypothesis that sex differences in maze learning result from sex differences in activity was tested with wild-caught prairie (Microtus ochrogaster) and meadow (M. pennsylvanicus) voles. For 38 voles error production and activity were simultaneously measured in a series of 7 symmetrical mazes. Repeated-measures analyses of variance (ANOVAS) examined species, sex, maze, and interaction effects for 3 dependent variables: errors, activity, and errors/activity. The pattern of significant effects was very different for the errors and activity ANOVAS, which suggests that differential activity cannot explain differential error rates. In contrast, the pattern of effects was very similar for errors and errors/activity ANOVAS, which suggests that controls for activity do not remove differences in error production. These results fail to support the activity hypothesis.

Animals↗
PubMed1987

Effects of postoperative environment on recovery of function after fimbria-fornix transection in the rat.

We have previously found that rats given dorsal hippocampus lesions show reduced deficits on maze learning, spontaneous alternation and extinction tasks when housed postoperatively in an "enriched" as opposed to an "impoverished" environment. In contrast, postoperative enriched conditions were ineffective in rats given bilateral entorhinal cortex lesions. In this study, we examined whether postoperative differential housing would reduce the impairment in radial maze performance induced by fimbria-fornix transections. Significant interactions were found between lesion state and housing condition for the total number of errors made, the number of errors on the first eight arms visited and for the number of arms visited before the first error in an 8-arm maze. The interaction was due to the fact that, in sham-operated rats, isolated ones made more errors than enriched counterparts whereas, in rats with lesions, enriched ones showed no improvement of performance in comparison to isolated counterparts. These data suggest that the integrity of fimbria-fornix pathways is an important factor for the expression of facilitated maze performance in intact enriched rats and in enriched rats with hippocampal system damage.

Animals↗
PubMed1992

Effects of physostigmine and scopolamine on rats' performances in object-recognition and radial-maze tests.

The effects of physostigmine and scopolamine were evaluated on working memory of rats in object recognition and radial-maze tests. Three doses of physostigmine hemi-sulfate (Phys: 0.05, 0.10 and 0.20 mg/kg), five doses of scopolamine hydrobromide (Scop: 0.125, 0.25, 0.5, 1.0 and 2.0 mg/kg), and one dose of scopolamine methylbromide (Mscop: 2.0 mg/kg) were used. In object recognition test, rats were submitted to three or four intertrial delay conditions (1-min, 15-min and either 60-min or 24-h). The higher doses of Scop (1.0 and 2.0 mg/kg) in 1-min and 15-min delay and of Phys (0.20 mg/kg) in 1-min delay impaired discrimination between new and familiar objects. Mscop impaired discrimination between objects in 60-min but not in 1-min and 15-min delay. This effect may be state dependent. Radial-maze learning was impaired by the lower doses of scopolamine (0.25 and 0.50 mg/kg) which had no effect in object recognition test. These results show that in our conditions, object recognition is less sensitive than radial-maze test to cholinergic drugs.

Analysis of Variance↗
PubMed1983

Learning impairments following postnatal exposure to benzene.

Two groups of male hooded rats of the Sprague-Dawley strain were administered 550 mg/kg of benzene in corn oil or pure corn oil on Days 9, 11, and 13 postpartum. When tested on problems of the Hebb-Williams closed-field maze-learning task, the rats previously exposed to benzene manifest significantly impaired learning ability when compared to control rats in the total number of error zones entered over the 12 test problems. No significant differences were found in food consumption, water consumption, or weight gain. Moreover, none of the overt manifestations characteristic of acute or chronic benzene exposure were observed. Learning deficits were exhibited at levels of exposure previously considered subtoxic.

Animals↗
PubMed1992

Relation of rotation to egocentric and allocentric spatial learning in the rat.

In this experiment, we asked whether the relation between amphetamine-induced rotation and the learning and retention of left-right discrimination extends to allocentric spatial learning or is limited to egocentric spatial tasks. Rotation was established following injections of d-amphetamine sulfate, and rats were classified as nonrotators, midrotators, or strong rotators. Animals were successively trained on navigation in the Morris water maze (allocentric) and delayed spatial alternation in a water T-maze (egocentric). There were no rotation effects in water maze learning but rotators and nonrotators differed significantly in delayed spatial alternation learning but not relearning. Strong rotators learned more slowly than midrotators, clearly implying that rotational bias and directional learning are not linearly related. We show that it is egocentric spatial learning that is facilitated by a nigrostriatal dopamine asymmetry and extend the generality of the left-right discrimination findings.

Amphetamine↗
PubMed1982

Residual learning capability in organic amnesia.

This article provides a review of residual learning capability in patients suffering from the organic amnesic syndrome. It is shown that organic amnesics are able to learn a considerable number of laboratory tasks, many to a level comparable with normals. It shown that the tasks on which they succeed invariably involve testing situations which do not refer to specific preceding events (e.g. pursuit rotor, maze learning, picture completion, conditioning). It is concluded that this pattern of preserved learning capability can be interpreted as an impairment of episodic storage with the relative sparing of what is often described as "semantic memory".

Alcohol Amnestic Disorder↗
PubMed1985

ACTH neuromodulation of the developing motor system and neonatal learning in the rat.

ACTH peptides influence the developing nervous system during the first three weeks of life in the rat. ACTH 4-10 and Org 2766 (10.0 micrograms/kg) accelerate the expression of motor hyperactivity usually exhibited in 15-day old normal animals, with ACTH 4-10 increasing the force of extensor digitorum longus muscle contraction amplitude. Following cold stress and peptide treatment, rate changes in motor activity from one age to the next are dramatically enhanced, with vertical activity being exhibited at an earlier age than controls. Grasping ability is similarly enhanced in 13-day old ACTH 4-10-treated animals. The retention of a T-maze learning paradigm is significantly enhanced in 16-day old ACTH 4-10 (10.0 micrograms/kg)-treated and Org 2766 (0.01 micrograms/kg)-treated animals, with these animals running the maze significantly faster than controls. Peptide treatment appears to reverse the apparent turning preference in the maze during extinction. It is suggested that ACTH peptides modulate the organization of the nervous system and facilitate neurotransmission, and may act on dopaminergic and cholinergic neurotransmitter systems. Motor behavior seems to reflect underlying neural substrates that are integrated to produce the overt behavior of the organism.

Adrenocorticotropic Hormone↗
PubMed2005

Modulation of memory and visuospatial processes by biperiden and rivastigmine in elderly healthy subjects.

RATIONALE: The central cholinergic system is implicated in cognitive functioning. The dysfunction of this system is expressed in many diseases like Alzheimer's disease, dementia of Lewy body, Parkinson's disease and vascular dementia. In recent animal studies, it was found that selective cholinergic modulation affects visuospatial processes even more than memory function. OBJECTIVE: In the current study, we tried to replicate those findings. In order to investigate the acute effects of cholinergic drugs on memory and visuospatial functions, a selective anticholinergic drug, biperiden, was compared to a selective acetylcholinesterase-inhibiting drug, rivastigmine, in healthy elderly subjects. METHODS: A double-blind, placebo-controlled, randomised, cross-over study was performed in 16 healthy, elderly volunteers (eight men, eight women; mean age 66.1, SD 4.46 years). All subjects received biperiden (2 mg), rivastigmine (3 mg) and placebo with an interval of 7 days between them. Testing took place 1 h after drug intake (which was around Tmax for both drugs). Subjects were presented with tests for episodic memory (wordlist and picture memory), working memory tasks (N-back, symbol recall) and motor learning (maze task, pursuit rotor). Visuospatial abilities were assessed by tests with high visual scanning components (tangled lines and Symbol Digit Substitution Test). RESULTS: Episodic memory was impaired by biperiden. Rivastigmine impaired recognition parts of the episodic memory performance. Working memory was non-significantly impaired by biperiden and not affected by rivastigmine. Motor learning as well as visuospatial processes were impaired by biperiden and improved by rivastigmine. CONCLUSIONS: These results implicate acetylcholine as a modulator not only of memory but also of visuospatial abilities.

Aged↗
PubMed2006

Single, intense prenatal stress decreases emotionality and enhances learning performance in the adolescent rat offspring: interaction with a brief, daily maternal separation.

Perinatal manipulations can lead to neurobehavioural changes in the progeny. In this study we investigated, in adolescent male rat offspring, the consequences of a single, intense prenatal stress induced by a 120 min-maternal immobilization at gestational day 16, and of a daily, brief maternal separation from postnatal day 2 until 21, on: unconditioned fear/anxiety-like behaviour in open field and in elevated plus-maze; learning performance in the "Can test", a non-aversive spatial and tactile/visual task; corticosterone plasma levels under basal and stress-induced conditions. Our results indicate that both prenatal stress and maternal separation procedures decrease emotionality and enhance learning performance. Maternal separation potentiates prenatal stress-induced effects in enhancing learning performance. Both basal and stress-induced corticosterone plasma levels are reduced following prenatal stress, maternal separation and the combination of two procedures. These findings suggest that a single, intense prenatal stress can enhance the adaptive stress-related responses in the progeny, probably due to the involvement of maternal factors. The synergistic effect of prenatal stress and maternal separation on learning performance may be due to a further damping of hypothalamic-pituitary-adrenal axis response in the progeny that better cope with the task administered.

Adaptation, Psychological↗
PubMed2002

Apolipoprotein E knockout mice display procedural deficits in the Morris water maze: analysis of learning strategies in three versions of the task.

Apolipoprotein E knockout (apoEKO) mice have been shown to be impaired in the spatial Morris water maze (MWM). However, several groups failed to replicate this finding. One reason for this inconsistency may stem from variations in the experimental protocols and environment between laboratories. In the present study, we have tested if age and variations in protocol implementation that specifically affect salience of the visual extramaze cues influence performance and navigational strategies in the MWM. We tested three- and 12-month-old apoEKO and wild type mice in three versions of the MWM differing on the availability of visual extramaze cues: (1) salient cues, (2) diffuse cues, and (3) absence of cues. Our results show that the presence of salient cues enhances acquisition performance of wild type, but not apoEKO mice in the MWM. This effect was restricted to the acquisition phase since apoEKO mice reached a level of performance that was comparable to that of controls toward the end of the task. No significant differences were detected between apoEKO and controls in either the diffuse cues or absence of cues paradigms. Thigmotaxic tendencies were observed in apoEKO mice and correlated high latency scores. Thigmotaxis may have interfered with the initial ability to engage in a proficient navigational strategy. These findings suggest that, in contrast to what has been proposed in the past, apoEKO mice appear not to be impaired in spatial memory per se but are deficient in a procedural component of the MWM. Furthermore, the procedural deficit and corresponding thigmotaxic tendencies of apoEKO mice appeared to increase with age. Taken together, these findings confirm our hypothesis that age and variations in experimental protocols can influence MWM performances.

Age Factors↗
PubMed2004

Impaired motor performance and learning in glia maturation factor-knockout mice.

Glia maturation factor (GMF) is a unique brain protein localized in astrocytes and some neuronal populations. Studies with overexpression of GMF using adenovirus vector have uncovered its regulatory role in intracellular signal transduction and downstream induction of biologically active molecules, including the neurotrophins and cytokines. The current paper deals with the behavior of mice devoid of GMF protein (knockout). GMF-null mice developed normally without gross abnormality. When tested for simple position discrimination using a T-maze and for spatial memory using a Morris water maze, the knockout mice performed as well as the wild-type, showing no defect in maze learning. However, with beam walking, GMF-knockout mice performed poorly and failed to learn. Knockout mice were also defective in learning the eyeblink classical conditioning. Histologically, the knockout mice showed a loss of neurons in the inferior olive, which is a component of the circuitry of eyeblink conditioning, and is also essential for motor performance. The structural abnormality in GMF-null mice explained their impaired ability for both motor performance and motor learning.

Animals↗