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PubMed1995

Effects of galanin on passive avoidance response, elevated plus-maze learning, and spontaneous alternation performance in mice.

The present study was done to characterize the effects of intracerebroventricular injection of galanin (GAL) on memory processes by observing passive avoidance response, elevated plus-maze learning, and spontaneous alternation performance in mice. An intermediate dose (3 micrograms) of GAL (3 micrograms) significantly decreased step-down latency of passive avoidance response when given 15 min before training, whereas in particular the middle doses (0.3 and 1 microgram) of GAL significantly decreased it when given 15 min before retention tests. However, GAL (0.3-10 micrograms) was ineffective when given immediately after training. Physostigmine (0.2 mg/kg), a cholinesterase inhibitor, and oxotremorine (0.01 and 0.03 mg/kg), a cholinergic agonist, significantly inhibited the shortening of step-down latency induced by GAL (0.3 microgram) administered 15 min before retention tests, indicating the involvement of cholinergic dysfunction in the GAL (0.3 microgram)-induced shortening of step-down latency. In contrast, GAL (0.3-3 micrograms) failed to influence transfer latency in elevated plus-maze learning or percent alternation in spontaneous alternation performance. These results suggest that the activation of cholinergic neurons improves memory dysfunctions induced by GAL, which primarily impairs retrieval processes of memory. The lack of effects of GAL on the elevated plus-maze learning and spontaneous alternation performance may result from the selective effects of GAL in different learning paradigms.

Amino Acid Sequence↗
PubMed1999

Sex and estrous cycle-dependent changes in neurosteroid and benzodiazepine effects on food consumption and plus-maze learning behaviors in rats.

Experiments were designed to investigate the influence of estrous cycle and gender of the rat on the effects of a gamma-aminobutyric acid type A (GABA(A)) receptor active neurosteroid, 3alpha-hydroxy-5alpha-pregnan-20-one (allopregnanolone), the benzodiazepine, triazolam, and a GABA(A) receptor antagonistic neurosteroid, delta5-androsten-3beta-ol-17-one sulfate (dehydroepiandrosterone sulfate), on food intake and elevated plus-maze learning behaviors. Allopregnanolone (0.25 mg/kg, s.c.) and triazolam (0.25 mg/kg, i.p.) produced a hyperphagic effect, while dehydroepiandrosterone sulfate (5 mg/kg, s.c.) elicited an anorectic effect. However, allopregnanolone was more potent in diestrous females, whereas triazolam exhibited significantly higher hyperphagic potency in estrus females. The extent of anorexia following dehydroepiandrosterone sulfate was alike in male and female rats. The triazolam- and allopregnanolone-induced hyperphagic effect was blocked by bicuculline (1 mg/kg, i.p.), a selective GABA(A) receptor antagonist. In contrast to triazolam, the hyperphagic effect of allopregnanolone was insensitive to flumazenil (5 mg/kg, i.p.), a benzodiazepine antagonist. Vehicle-treated diestrous rats displayed moderately higher latencies in the elevated plus-maze learning task than estrus or proestrus females. Although allopregnanolone and triazolam elicited equipotent learning deficits in plus-maze learning in male and female rats, the magnitude of impairment-induced by triazolam was significantly higher in diestrous females than proestrus females. Dehydroepiandrosterone sulfate enhanced memory performance only in male rats. Although the use of the elevated plus-maze as a learning paradigm with benzodiazepines and neurosteroids may be sensitive to changes in anxiety, the differential data suggest that neurosteroid-induced effects are at least partly specific to learning behavior. These results confirm the role of estrous cycle and sex of rats in modifying the potency of neurosteroids and benzodiazepines on food consumption and learning and memory processes.

Analysis of Variance↗
PubMed1999

Maze learning impairment is associated with stress hemopoiesis induced by chronic treatment of aged rats with human recombinant erythropoietin.

Mean cell volume (MCV) of erythrocytes has been reported to increase with age in humans, and to be negatively correlated with memory performance in humans and rats. We evaluated hematological changes in 21-mo old male Fischer 344 rats undergoing a 3-mo twice weekly subcutaneous injection of human recombinant erythropoietin (EPO). A baseline hematocrit (HCT) was obtained initially and repeated at monthly intervals to determine the effectiveness of EPO treatment. At 24-mo of age and after 3 mo EPO treatment, the rats were tested for their ability to learn a 14-unit T maze. Following maze testing, blood was drawn for hematologic analyses, including HCT, MCV, maximum swollen cell volume (MCVS), mean cell transit time (MCTT), and the membrane shear modulus of elasticity (G), the latter a derived measure of the relative elasticity of the red cell membrane. After 1 mo EPO treatment, HCT significantly increased compared to saline-injected controls. After 2 mo treatment, HCT began to decline but remained elevated above baseline levels even after 3 mo treatment. After 3 mo EPO treatment, MCV was significantly lower in EPO-treated rats compared to controls. These changes imply altered hemopoiesis to produce cells which undergo shrinkage associated with accelerated cellular aging. The lower MCV would have predicted a shorter MCTT which instead was unchanged. This observation suggested the presence of an additional factor contributing to the MCTT. The G, which measures the membrane contribution to deformability, very significantly increased with EPO treatment. This finding indicates an increased contribution of membrane properties to the MCTT after EPO treatment, which cancels the expected decrease in MCTT for smaller cells. After 3 mo of EPO treatment, aged rats exhibited significantly impaired maze learning compared to controls. A relationship between, changes in erythrocyte membrane properties and impaired function was indicated by a significant correlation (r=0.67, p <0.04) between G and errors in the 14-unit T-maze. These findings suggest that stress-induced erythropoiesis produces accelerated aging in the red blood cell population that may have functional implications (i.e., impaired learning ability).

Aging↗
PubMed1999

A long-term stress exposure impairs maze learning performance in rats.

To elucidate hippocampal dysfunctions following chronic stress exposure, we evaluated the effect of chronic stress on maze learning performance, as assessed by a radial eight-arm maze task. In the 12-week stress sessions, male rats in the stress group were exposed to the stress of a 15-min immersion in cold water once a day and, rats in the control group were slightly handled. Rats in the stress group performed significantly poorly during the acquisition period (P < 0.01) and required more trials to attain at least seven correct choices in the first eight choices for five consecutive trials (P < 0.05). Together with our previous findings that chronic stress exposure damages the hippocampus histologically, we concluded that chronic stress exposure resulted in an impairment of maze learning performance, probably due to hippocampal damages.

Animals↗
PubMed2001

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.

Animals↗
PubMed2002

Dose-response effect of egg-phosphatidylcholine on maze-learning ability and fatty acid composition of plasma and brain in aged mice fed an n-3 fatty acid-deficient diet.

BACKGROUND/AIMS: We investigated the dose-response effect of egg-phosphatidylcholine (PC) on the maze-learning ability and brain fatty acid composition in aged mice. METHOD: Male Crj:CD-1 mice aged 18 months were fed the following diets for 4 months: (i) 5 g palm oil/100 g diet (n-3-deficient control group); (ii) 1 g egg-PC/100 g diet plus 4 g palm oil/100 g diet (egg-PC 1% group); (iii) 2.5 g egg-PC/100 g diet plus 2.5 g palm oil/100 g diet (egg-PC 2.5% group), and (iv) 5 g egg-PC/100 g diet (egg-PC 5% group). Maze-learning ability was assessed 3 months after the start of the experiment. All animals were maintained on the n-3 fatty acid-deficient diets to examine the direct effect of egg-PC on maze behavior. The time required to reach the maze exit and the number of times that a mouse strayed into blind alleys in the maze were measured in 3 trials every 4 days. RESULTS: Our results showed that the 2.5 and 5% egg-PC groups needed less (p < 0.05) time to find the exit and strayed into blind alleys fewer times (p < 0.05) than the control group. In order to determine the relationship between maze-behavior and brain docosahexaenoic acid (DHA) and arachidonic acid (AA) levels in aged mice fed various doses of egg-PC, the plasma and brain fatty acid composition was examined. Dose-response increases in the percentage of DHA were found in plasma lipids. However, based on our data on the brain fatty acid composition of mice fed various doses of egg-PC, no significant differences in the percentages of DHA and AA among the dietary groups were observed. CONCLUSION: These results suggest that the intake of egg-PC improves maze-learning ability in aged mice fed n-3 fatty acid-deficient diets but it does not influence the percentage of brain DHA and AA.

Aging↗
PubMed1999

Stress impairs performance in spatial water maze learning tasks.

The water maze task has been developed to test spatial learning abilities in rats or mice, and is widely used. Though it has been reported before that numerous cognitive abilities are of importance for learning this task, poor performance is usually interpreted as an impairment of spatial memory formation. Previous investigations that tried to correlate long-term potentiation (LTP) of synaptic transmission with spatial learning abilities in rats reported that injection of drugs or specific gene deletions which blocked the expression of LTP correlated with learning impairments of spatial tasks in a water maze. Recent studies, however, have shown that pretraining enables these animals to learn such spatial tasks even though LTP was still found to be blocked. I investigated to what degree altered fear condition and stress perception could account for the impaired spatial learning when no pretraining is given. In a fear habituation task, unhandled rats preferred a dark over a well lit chamber more than handled animals did, but unhandled rats favoured the lit chamber more in an active avoidance task. They also performed poorly in a spatial water maze task compared with handled rats. Rats pretrained in a radial arm maze performed better in a water maze than non-pretrained rats. No difference between groups was found in a non-spatial water maze task. On the other hand, when pretrained in a water maze, rats performed only marginally better in a radial arm maze compared to non-pretrained animals. Since animals have to be handled to learn a radial arm maze, the difference in this task was not due to stress but most probably due to getting accustomed to the room dimensions prior to learning the spatial task. The results suggest that impaired learning of spatial tasks in the water maze can be due to increased stress and decreased fear conditioning without actually affecting spatial learning abilities. These results question the interpretations of the results of some previously published results of spatial water maze tasks.

Animals↗
PubMed2002

A link between maze learning and hippocampal expression of neuroleukin and its receptor gp78.

Neuroleukin (NLK) is a multifunctional protein involved in neuronal growth and survival, cell motility and differentiation, and glucose metabolism. We report herein that hippocampal expression of NLK and its receptor gp78 is associated with maze learning in rats. First, mRNA levels of NLK and gp78 were significantly increased in hippocampi of male Fischer-344 rats following training in the Stone T-maze and the Morris water maze. Second, a parallel increase was found in hippocampal NLK and gp78 proteins after maze learning. Third, NLK and gp78 mRNA and protein expression in hippocampus was reduced in a group of aged rats that showed more errors during the acquisition of the Stone maze task as compared with young rats. Finally, application of recombinant NLK to hippocampal neurons significantly enhanced glutamate-induced ion currents, functional molecular changes that have been correlated with learning in vivo. Taken together, our results identify a novel association of hippocampal expression of NLK and its receptor gp78 with rat maze learning. Interaction of NLK with gp78 and subsequent signaling may strengthen synaptic mechanisms underlying learning and memory formation.

Aging↗
PubMed1987

Basal forebrain infusion of HC-3 in rats: maze learning deficits and neuropathology.

Ten adult male Sprague-Dawley rats were infused with hemicholinium (HC-3) using mini-osmotic pumps over a 14 day period through bilateral, chronically implanted cannulae in the nucleus basalis magnocellularis (nbm). Ten matched controls were infused in the same fashion with saline. HC-3 rats receiving implants demonstrated a significant deficit in maze-learning ability compared with individual and group performances before receiving the implants. In saline rats there was no significant difference in maze-learning ability before and after receiving implants. The HC-3 group receiving implants demonstrated a significant deficit in maze-learning ability compared with the saline control group. Serial sections through nbm from control and HC-3 rats indicated that all cannulae were located within infusion range of nbm. In HC-3 subjects, cholinergic cell bodies were destroyed with concurrent degeneration of terminal fields in cortex. Except for cannula insertion damage, the cholinergic neurotransmitter system appeared unharmed in controls. Stains for neuritic plaques and neurofibrillary damage were negative in both groups. The memory deficit in experimental subjects supported by the demonstrated destruction of nbm cholinergic neurons suggests that HC-3 may be useful in the development of an animal model for Alzheimer's Disease.

Animals↗
PubMed1992

Learning behaviour in chronic vitamin E-deficient and -supplemented rats: radial arm maze learning and passive avoidance response.

The effects of long-term vitamin E deficiency and supplementation on learning behaviour were investigated. Rats were fed vitamin E-deficient [VE(-)], -supplemented [VE(+)], or control standard food beginning after the age of 4 weeks. They were trained in an eight-arm radial maze learning task at the age of 17 months, and in a step-through passive avoidance response (PAR) task at the age of 25 months. In the radial maze task, both VE(-) and VE(+) animals required as many trials to reach the learning criterion as control animals. Scopolamine injection (0.25-0.5 mg/kg) after acquisition of the task decreased the number of correct choices dose-dependently; however, the degree of the drug effect on VE(-) and VE(+) rats did not differ from that on control rats. On the other hand, VE(-) animals showed significantly lower rate of avoidance response and VE(+) animals tended to show higher rate of avoidance response in the PAR task than did control animals. These results suggest that long-term vitamin E deficiency or supplementation does not influence general ability to acquire and maintain memory tasks in rats, but that it may affect learning behaviour, depending on the kind of task in which animals were trained.

Age Factors↗
PubMed2004

Comparison of the role of somatosensory stimuli in maze learning in a blind subterranean rodent and a sighted surface-dwelling rodent.

We compared the role of tactile perception in maze learning in the blind mole rat and in the laboratory rat. Both species were tested in each of two mazes that were identical in complexity but differed in tunnel width and height: the first was only slightly wider than the animal's body width (narrow maze) while the second was about twice the animal's body width (wide maze). We found that the performances of rats tested in the narrow maze were significantly lower than those tested in the wide maze, as measured by time and number of errors to reach the end of the maze (food reward). The mole rats, in contrast, performed significantly better in the narrow maze than in the wide maze. Further, in contrast to the rats, the mole rats' locomotion in the wide maze was much less continuous than in the narrow maze, reflected in longer and more frequent stops at maze junctions, where they pressed the side of their body tightly against the tunnel walls. Two main conclusions are derived from this experiment. First, subterranean mammals, such as the blind mole rat, appear to rely more on tactile stimuli while exploring and learning a complex maze than do sighted surface-dwelling rodents, such as rat. The extensive use of this somatosensory channel may compensate for the mole rats' visual deficiency, and thus substantially contribute to their excellent spatial orientation ability, previously demonstrated in field and laboratory conditions. Second, poor performance of surface-dwelling rodents, such as the rats, in spatial-maze learning tasks might not be a consequence of impaired cognitive learning ability, but rather due to testing the animal in a physical situation that does not provide the necessary somatosensory stimuli found in their natural habitat.

Animals↗
PubMed1997

Effects of Tyr-D-Arg-Phe-beta-Ala-NH2, a novel dermorphin analog, on elevated plus-maze learning and spontaneous alternation performance in mice.

1. The effects of intracerebroventricular administration of Tyr-D-Arg-Phe-beta-Ala-NH2 (TAPA), a novel dermorphin analog, on plus-maze learning and spontaneous alternation performance were investigated in mice. 2. The pre- or posttraining or preretention administration of TAPA (0.3-3.0 ng) alone failed to affect transfer latency of plus-maze learning, whereas TAPA (3 ng) produced a significant decrease in percent alternation without affecting total arm entries. 3. beta-Funaltrexamine (5 micrograms) almost completely reversed the TAPA (3 ng)-induced decrease in percentage of alternation. 4. These results suggest that stimulation of mu-opioid receptors disrupts spontaneous alternation performance associated with spatial working memory.

Analgesics, Opioid↗
PubMed1994

Comparison of four spatial maze learning tests with methylnitrosourea-induced microcephaly rats.

The usefulness of four spatial maze learning test methods, single T-maze, Biel water maze, Morris water maze, and radial eight-arm maze, was compared using rats with different degrees of microcephaly, which were induced by single intraperitoneal injection with 3 and 5 mg/kg of methylnitrosourea (MNU) on day 13 of gestation. The single T-maze test did not detect a learning defect in either MNU group. In the Biel water maze test, the swimming time and number of errors were increased in the 5 mg/kg group, but these parameters were comparable to the control values in the retention and path B (reverse course) tests. On the Morris water maze task, the 5 mg/kg group required longer swimming time and distance to reach the goal. In the retest with the goal set on an opposite side, the swimming distance in the 5 mg/kg group was as long as the value in the original test. The radial eight-arm maze test detected fewer correct choices in both MNU groups, which showed different responses on this task. The brain weights in the 3 and 5 mg/kg groups were approximately 80 and 60% of the control value, respectively. The cerebral cortex weights were 77 and 50% of the control value, and the hippocampus weights were 78 and 51%. Among the four maze tests, only the radial eight-arm maze test could detect the effect of both doses of MNU. This shows that the method has the highest sensitivity to spatial learning defect in MNU-induced microcephalic rats.

Abnormalities, Drug-Induced↗
PubMed1989

Chicks' maze learning reinforced by visual pitfall extending downward.

The present study examined whether visually evoked fear of depth could reinforce a particular response of animals, i.e., to special maze learning. The maze was composed of four units of Y-shaped alley. In this maze, the visual pitfalls were set behind corners of the alley in place of a physical barrier. The experiments showed that eight of 13 male chicks could achieve the initial learning and that three successful ones could also achieve reversal learning. The results suggest that the visually evoked fear of depth provided by motion parallax can act as a reinforcer.

Animals↗
PubMed2000

Sex differences in vicarious trial-and-error behavior during radial arm maze learning.

We investigated sex differences in VTE behavior in rats during radial arm maze learning. Females made more VTEs than males, although there were no sex differences in learning. Further, VTEs and errors were positively correlated during the latter testing sessions in females, but not in males. This sex difference may be a reflection of differences between the sexes in conflict behavior or cognitive strategy while solving the maze.

Animals↗
PubMed1999

Radial maze learning in two inbred mouse strains and their reciprocal congenics for the non-pseudoautosomal region of the Y chromosome.

The effect of the non-pseudoautosomal region of the Y chromosome on spatial learning in a radial maze task was examined in two inbred mouse strains, NZB and CBA/H, and their respective congenics for the Y(NPAR). Seven variables reflecting learning performance, learning strategy and lateralisation were measured. We found no substantial effect of the Y(NPAR) on radial maze learning, but modest influences on behavioral strategies. These findings are in agreement with previous results regarding the sizes of the intra- and infrapyramidal mossy fiber (IIPMF) terminal fields.

Animals↗
PubMed2002

Lateralization of spatial-memory processes: evidence on spatial span, maze learning, and memory for object locations.

Spatial memory is one of the most important cognitive functions in daily life, enabling us to locate objects in our environment or to learn a route or a path. In the present study, we elaborated on the hypothesis that human spatial memory consists of multiple sub-processes, relying on different brain structures. Therefore, 50 patients with an ischemic stroke and 40 healthy participants underwent tests measuring spatial span and maze learning. By means of a computer paradigm the following aspects of memory for object locations were assessed: (1) object location binding; (2) positional memory; (3) a combination of these two aspects. The results clearly showed a double dissociation: the group of patients with an infarct in the left hemisphere (LH) was impaired on object location binding, whereas the group with an infarct in the right hemisphere (RH) was impaired on positional memory. Lesions in the RH resulted also in impairments on maze learning. Moreover, patients with lesions in the posterior part of the parietal or the occipital lobe performed especially worse on spatial-memory tasks. These findings extend the theoretical framework of categorical versus coordinate spatial processing in the human brain and corroborate previous findings on selective aspects of memory for object locations.

Adult↗
PubMed1986

[Effects of maternal alcohol exposure during gestation and/or lactation periods on radial-maze learning in offspring rats].

The present study was designed to investigate the effects of maternal alcohol (15%) exposure during the gestation and/or lactation periods on learning of an 8-arm radial maze by rat offspring. Acquisition of the maze learning was found to be profoundly retarded only in the offspring of mothers treated with alcohol during gestation. This result could not be explained by a secondary effect of malnutrition produced by the alcohol treatment, because body weight increase in the offspring was suppressed by the alcohol treatment during lactation but not during gestation. The possibility of involvement of deficits in brain development (especially of the hippocampus) in the learning impairment was discussed.

Animals↗