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PubMed2001

[Possible mechanisms in latent learning formation investigated by using mutant mice].

We examined possible mechanisms in the development of latent learning by methods of behavioral pharmacology and confirmed them by using mutant mice. Mice that received dopamine agonists, a noradrenergic neurotoxin or a traumatic brain injury showed impairment of latent learning. This impairment was suggested to be mediated by imbalance of dopaminergic and noradrenergic systems since the impairment was attenuated by a noradrenaline uptake inhibitor or a dopamine-D2 antagonist. The heterozygous mice for the tyrosine hydroxylase (TH) gene and for the cyclic AMP (cAMP) response element binding protein (CREB) binding protein (CBP) gene showed impairment of latent learning in the water finding task. The spatial learning and hippocampal long-term potentiation (LTP) were normal in both the mutants. TH heterozygous mice showed a reduction of high K(+)-evoked noradrenaline release in the frontal cortex by the microdialysis technique and a reduction of cAMP of the brain cAMP content. The central noradrenergic systems and/or cAMP signal pathways play an important role in latent learning, but not spatial memory. In contrast with TH and CBP mutant mice, nociceptin-knockout mice showed an enhanced retention of latent learning in the water finding task, greater learning ability in the water maze task and larger LTP than wild-type mice. Such mice showed hyperfunction of dopaminergic systems in the cortex. Nociceptin itself induced latent learning impairment in wild-type mice. These results suggest that the nociceptin system seems to play negative roles in learning and memory. In conclusion, the results of mutant mice further supported our previous results of behavioral pharmacology and suggest that the alternation of catecholamine biosynthesis and cAMP signal pathways may play a key role in development of latent learning. They further suggest that the expression of genes mediated by phosphorylated CREB may be involved in the development of latent learning.

Adenylyl Cyclases↗

PubMed1999

Blockade of N-methyl-D-aspartate receptors in the insular cortex disrupts taste aversion and spatial memory formation.

The present experiments examined the effects of direct intracortical microinjections of the N-methyl-D-aspartate receptor antagonist 2-amino-5-phosphonovaleric acid directly into the insular cortex of rats, before or immediately after training of conditioned taste aversion and the water maze spatial learning task. In the first series of experiments animals received bilateral injections of 2-amino-5-phosphonovaleric acid prior to taste aversion conditioning or spatial training. A strong disruptive effect was found in the acquisition of training tasks. To determine the possible involvement of N-methyl-D-aspartate receptors in the early post-training processes taking place in the cortex during both learning paradigms, in a second series of experiments, animals received bilateral 2-amino-5-phosphonovaleric acid microinjections 30, 60 or 120 min after the acquisition trial, and 15 min before the retention test. For spatial learning successive treatments were independently done either starting at the onset of the asymptotic phase of the learning curve, 0, 30 or 120 min after finishing the training session, as well as 15 min before the retention test trial. The conditioned taste aversion task remained sensitive to N-methyl-D-aspartate blockade during a period of at least 2 h after the first presentation of the gustatory stimulus, while in the case of the spatial learning task, a gradually decreasing effect was observed from the onset of the asymptotic phase onwards. Taken together, these results provide direct evidence for N-methyl-D-aspartate receptor involvement in cortical regulation of memory formation. Furthermore, our results suggest that in the same cortical region, a different time-course for the activation of N-methyl-D-aspartate-dependent mechanisms occurs during the early formation of cortically mediated memories, depending on the particular behavioural task.

2-Amino-5-phosphonovalerate↗

PubMed2000

Hippocampal mossy fibers and swimming navigation learning in two vole species occupying different habitats.

We showed previously for mice that size differences of the infrapyramidal hippocampal mossy fiber projection (IIP-MF) correlate with spatial learning abilities. In order to clarify the role of the IIP-MF in a natural environment, we studied the bank vole (Clethrionomys glareolus), adapted to a wide range of different habitats, and the root vole (Microtus oeconomus), living in homogenous grassland habitats with small home ranges. Morphometry on Timm-stained horizontal brain sections of six C. glareolus and six M. oeconomus revealed that the size of the entire mossy fiber projection was 42% larger in C. glareolus than M. oeconomus. C. glareolus had also an IIP-MF projection about 230% larger than that of the root vole. A sample of captured animals was then transferred to the laboratory (C. glareolus, n = 23; M. oeconomus, n = 15) and underwent testing for swimming navigation according to a standardized protocol used to assess water maze learning in about 2,000 normal and transgenic mice. Both species learned faster than laboratory mice. Overall escape times showed no differences, but path length was significantly reduced in C. glareolus, which also showed superior performance in a variety of scores assessing spatial search patterns. On the other hand, M. oeconomus showed faster swimming speed, and strong thigmotaxis combined with circular swimming. M. oeconomus also scored at chance levels during the probe trial, about as poorly as mutant knockout mice considered to be deficient in spatial memory. These differences probably reflect differential styles of water maze learning rather than spatial memory deficits: C. glareolus appears to be superior in inhibiting behavior interfering with proper spatial search behavior, while M. oeconomus succeeds in escaping by using rapid circular swimming. We assume that size variations of the IIP-MF correspond to a mechanism stabilizing hippocampal processing during spatial learning or complex activities. This corresponds to the ecological lifestyle of the two species and is in line with previous observations on the role of the IIP-MF.

Animals↗

PubMed2005

Motherhood mitigates aging-related decrements in learning and memory and positively affects brain aging in the rat.

The current work examined spatial learning and memory (i.e., latencies to find a baited food well) in age-matched nulliparous, primiparous and multiparous (NULL, PRIM and MULT, zero, one or two pregnancies and lactations, respectively). We tested at 6, 12, 18 and 24 months of age in a dry land version of the Morris water maze (Main task), and at 12, 18 and 24 months in the same task in which the original location of the baited well was changed (Reversal task). We show that PRIM/MULT rats, compared to the age-matched NULL females, learned the spatial tasks significantly better and exhibited attenuated memory decline, up to 24 months of age. Furthermore, at the conclusion of behavioral testing, we investigated levels of these animals' hippocampal (CA1 and dentate gyrus) immunoreactive amyloid precursor protein (APP), a marker of neurodegeneration and age-related cognitive loss. MULTs had significantly reduced APP in both CA1 and DG, relative to PRIMs and NULLs, and PRIMs had a trend (p<0.06) toward a reduction in APP compared to NULLs in DG. Further, level of APP was negatively correlated with performance in the two tasks (viz., more APP, worse maze performance). Reproduction, therefore, with its attendant natural endocrine and postpartum sensory experiences, may facilitate lifelong learning and memory, and may mitigate markers of neural aging, in the rat. Combining natural hormonal exposure with subsequent substantial experience with stimuli from the offspring may preserve the aged parous female brain relative to that of NULL females.

Age Factors↗

PubMed1998

Effect of traumatic brain injury on mouse spatial and nonspatial learning in the Barnes circular maze.

Controlled cortical impact (CCI) is a relatively new model of traumatic brain injury in the mouse, which, in combination with behavioral and histological methods, has potential for elucidating underlying mechanisms of neurodegeneration using genetically altered animals. Previously, we have demonstrated impaired spatial learning in a water maze task following CCI injury at a moderate level. There are many difficulties associated with this task, however, such as stress, physical demand, and the multiple trials over days required for satisfactory training. As a potential alternative to the water maze, we adapted the Barnes circular maze to our mouse model and assessed spatial/nonspatial learning following injury. Mice were trained to locate a dark tunnel, hidden beneath one of 40 holes positioned around the perimeter of a large, flat, plastic disk, brightly illuminated by four overhead halogen lamps. Sham-operated animals rapidly acquired this task, exhibiting reduced latency to find the tunnel and a more efficient search strategy as compared with injured mice. This difference was not due to visuomotor deficits, as all mice performed equally well in a cued version of the same task. These results demonstrate spatial learning impairment following CCI injury in a task that offers an efficient alternative to the water maze.

Acute Disease↗

PubMed1994

The NMDA-receptor antagonist MK-801 impairs navigational learning in homing pigeons.

The present study employed the N-methyl-D-aspartate (NMDA) receptor antagonist MK-801 to investigate the possible importance of NMDA receptor activation for naturally occurring spatial learning in birds by exploiting the navigational ability of homing pigeons (Columba livia). Control pigeons released from two unfamiliar release sites displayed vanishing bearings that were poorly oriented. However, when released a second time from the same sites they displayed improved homeward orientation. The control birds apparently learned something about the spatial relationships of stimuli at the release sites on the first releases and used that information to orient better when released a second time from the same locations. Experimental pigeons given the NMDA receptor antagonist MK-801 (0.10 mg/kg) initially behaved as controls, orienting poorly when released for the first time from the two sites. In contrast to controls, the experimental birds failed to show significant improvement in orientation when released again from the same sites without MK-801. A second experiment revealed no state-dependent learning. Results of a position/color discrimination task showed that the impairments observed did not generalize to associative learning in an operant chamber, and together with field observations were not a result of sensory or motor drug effects. The data indicate that blocking NMDA receptors can disrupt navigational learning in homing pigeons. As such, the results are consistent with the hypothesis that NMDA receptor activation plays an important role in spatial learning in birds.

Animals↗

PubMedDate not supplied

Learning and memory in rats gestationally and lactationally exposed to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD).

Recently we reported that in utero and lactational exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) or coplanar polychlorinated biphenyls (PCBs) resulted in a reduction of errors on a radial arm maze (RAM) working memory task. The effect was more pronounced in males than in females. In this study, we further investigated the effects of in utero and lactational exposure to TCDD on learning and memory by testing male and female TCDD-exposed rats on three different spatial learning and memory tasks: the RAM, the Morris water maze (MWM), and spatial discrimination-reversal learning (RL), as well as on a nonspatial learning task, visual RL. Time-mated Sprague-Dawley rats were gavaged with either TCDD (0.1 microg/kg/day) or corn oil vehicle on gestation days 10-16. Litters were culled to eight on day 2 and weaned on day 21. Beginning on day 80, one male and one female from each litter were tested on the same RAM working memory task used in the previous study. Again, the TCDD-exposed male rats displayed a pronounced decrease in errors relative to control males. Following the RAM testing, the same animals were tested on the MWM, but no differences between the exposed and control rats were observed. Another male and female from each litter were tested on spatial RL on a T-maze. There were no differences between the exposed and control rats on this task. Following spatial RL, the same rats were tested on visual RL on the same maze. The exposed animals did not differ from controls on original learning, but took more trials to reach criterion on the first and second reversals. These results demonstrate a reliable, but task-specific, facilitation of spatial learning and memory in male rats exposed to TCDD during gestation and lactation. In contrast, both male and female TCDD-exposed rats showed a deficit in learning on the visual RL task. This pattern is consistent with that seen in earlier monkey studies. Perinatally TCDD-exposed monkeys were facilitated on certain spatial tasks, but impaired on visual RL tasks.

Analysis of Variance↗

PubMed2000

Water maze and radial maze learning and the density of binding sites of glutamate, GABA, and serotonin receptors in the hippocampus of inbred mouse strains.

Correlations between the densities of ionotropic glutamate, GABA(A), and serotonin binding sites in the hippocampus of seven inbred mouse strains and strain-specific learning capacities in two types of maze were studied. Binding site densities were measured with quantitative receptor autoradiography. Learning capacities were determined in a water maze task as well as in spatial and nonspatial versions of an eight-arm radial maze. The densities of most binding sites differed significantly between the strains in the subfields of Ammon's horn (CA1 and CA3) and the dentate gyrus, except for serotonin binding sites in CA1. By comparing the different strains, significant receptor-behavioral correlations between the densities of the GABA(A) receptors and the activity-dependent behavior in the water maze as well as the spatial learning in the radial maze were found. The densities of D,L-alpha-amino-3-hydroxy-5-methyl-4-isoxalone propionate (AMPA) and kainate receptors correlated positively with learning capacity in the spatial eight-arm radial maze. We conclude that hereditary variations mainly in AMPA, kainate, and GABA(A) receptor densities are involved in behavioral variations in spatial and nonspatial learning tasks.

Analysis of Variance↗

PubMed1998

Modulation of acetylcholine and serotonin transmission by galanin. Relationship to spatial and aversive learning.

This paper presents evidence that galanin is a potent in vivo modulator of basal acetylcholine release in the rat brain with qualitatively and quantitatively differential effects in the dorsal and ventral hippocampus. Galanin perfused through the microdialysis probe decreased basal acetylcholine release in the ventral hippocampus, while it enhanced acetylcholine release in the dorsal hippocampus. Galanin (3 nmol/rat) infused into the ventral hippocampus impaired spatial learning acquisition, while it tended to facilitate acquisition when injected into the dorsal hippocampus. These effects appear to be related to activation of GAL-R1 (ventral hippocampus) and GAL-R2 (dorsal hippocampus) receptors, respectively. However, the effects of galanin on acetylcholine release and on spatial learning appear not to be directly related to cholinergic mechanisms, but they may also involve interactions with noradrenaline and/or glutamate transmission. Galanin administered into the lateral ventricle failed to affect acetylcholine release, while this route of administration produced a long-lasting reduction in 5-HT release in the ventral hippocampus, indicating that galanin is a potent inhibitor of mesencephalic 5-HT neurotransmission in vivo. Subsequent studies supported this hypothesis, showing that the effects on 5-HT release in vivo are most likely mediated by a galanin receptor in the dorsal raphe. The implications of these findings are discussed in relation to the role of acetylcholine in cognitive functions in the forebrain and the role of the raphe 5-HT neurons in affective disorders.

Acetylcholine↗

PubMed2004

Spatial conditional associative learning: effects of thalamo-hippocampal disconnection in rats.

Unilateral lesions to the anterior thalamic nuclei (ATN) and the hippocampus (H) were made in opposite hemispheres in the rat to examine whether these brain structures form part of a functional neural pathway underlying spatial learning and memory. In the first experiment, rats were tested on a spatial-visual conditional associative task in which they had to learn to approach one of two stimuli depending on the spatial context in which the stimuli were embedded. The rats were subsequently trained on delayed forced alternation, a spatial working memory task known to be sensitive to the effects of ATNxH damage. Rats with ATNxH lesions were impaired in the acquisition of both tasks in comparison with normal control animals. The findings support the idea that the anterior thalamic nuclei and the hippocampus are critical components of an anatomical system subserving spatial memory and suggest that these brain regions work in a dependent fashion during the performance of certain spatial learning tasks.

Analysis of Variance↗

PubMed2005

Behavioural profiles of inbred mouse strains used as transgenic backgrounds. II: cognitive tests.

One of the characteristic manifestations of several neurodegenerative diseases is the progressive decline in cognitive ability. In order to determine the suitability of six mouse strains (129S2/Sv, BALB/c, C3H/He, C57BL/6j, CBA/Ca and DBA/2) as transgenic background strains, we investigated the performance on a variety of tasks designed to identify subtle changes in cognition. In addition, a test of exploratory behaviour was used to probe the level of underlying anxiety in these mouse strains, as anxiety can be a confounding factor on behavioural performance generally. The C3H/He mice exhibited the least anxiogenic behavioural profile spending most time on the open arms of the maze, in contrast to the 129S2/Sv mice which spent the least amount of time in this location and were the quickest to move into a closed arm. The C3H/He mouse strain failed to acquire a visual discrimination task and failed to demonstrate learning on a water maze spatial learning task, in contrast to the CBA/Ca, DBA/2 and C57BL/6j strains which demonstrated a degree of learning in both tasks. No significant strain differences were identified on the object recognition task. These data, taken together, suggest that care must be taken when choosing cognitive tasks to be used with particular mouse strains and that task sensitivity must be considered as a critical element to research protocols with regard to these mouse strains.

Analysis of Variance↗

PubMed1998

Effect of a prolyl endopeptidase inhibitor, JTP-4819, on radial maze performance in hippocampal-lesioned rats.

The effect of a novel prolyl endopeptidase (PEP) inhibitor, (S)-2-2[[(S)-2-(hydroxyacetyl)-1-pyrrolidinyl]carbonyl]-N-(phenylmethyl) -1-pyrrolidinecarboxamide (JTP-4819), on spatial learning deficits in rats with dorsal hippocampal (DH) lesions was examined using an eight-arm radial maze. The correct performance remained at chance levels even after 18 acquisition trials in rats with DH lesions. JTP-4819 (3.0 mg/kg, p.o.) significantly ameliorated this learning impairment after 34-41 days of treatment. When DH lesions were created in rats after achievement of learning, postoperative performance deteriorated prominently, but gradually recovered with the repetition of trials. JTP-4819 (3.0 mg/kg, p.o.) significantly decreased the number of trials needed to reattain learning criterion. After the behavioral experiment, the choline acetyltransferase (ChAT) activity and [3H]-pirenzepine binding (Kd, Bmax) in the residual hippocampus and cerebral cortex were analyzed. Neither parameter was significantly affected by JTP-4819. In conclusion, JTP-4819 can improve both learning and relearning deficits of spatial memory in DH-lesioned rats, postulating that enhancement of neuropeptide activity via PEP inhibition may be involved in the mechanism of action of JTP-4819.

Animals↗

PubMed1997

Role of estrogen replacement therapy in memory enhancement and the prevention of neuronal loss associated with Alzheimer's disease.

Recent evidence supports a role for estrogens in both normal neural development and neuronal maintenance throughout life. Women spend 25-33% of their life in an estrogen-deprived state and retrospective studies have shown an inverse correlation between dose and duration of estrogen replacement therapy (ERT) and incidence of Alzheimer's disease (AD), suggesting a role for estrogen in the prevention and/or treatment of neurodegenerative diseases. To explore these observations further, an animal model was developed using ovariectomy (OVX) and ovariectomy with estradiol replacement (E2) in female Sprague-Dawley rats to mimic postmenopausal changes. Using an active-avoidance paradigm and a spatial memory task, the effects of estrogen deprivation were tested on memory-related behaviors. OVX caused a decline in avoidance behavior, and estrogen replacement normalized the response. In the Morris water task of spatial memory, OVX animals showed normal spatial learning but were deficient in spatial memory, an effect that was prevented by estrogen treatment. Together these data indicate that OVX in rats results in an estrogen-reversible impairment of learning/memory behavior. Because a plethora of information has been generated that links decline in memory-related behavior to dysfunction of cholinergic neurons, the effects of estrogens on cholinergic neurons were tested. We demonstrated that OVX causes a decrease in high affinity choline uptake and choline acetyltransferase activity in the hippocampus and frontal cortex; ERT reverses this effect. Further, we showed that estrogens promote the expression of mRNA for brain-derived neurotrophic factor (BDNF) and nerve growth factor (NGF), 2 neurotrophic substances that have been shown to ameliorate the effects of age and injury on cholinergic neurons. Tissue culture models were used to evaluate whether estrogen treatment increases the survival of neurons when exposed to a variety of insults. 17-beta-Estradiol (beta-E2) protects cells from the neurotoxic effects of serum deprivation and hypoglycemia in human neuroblastoma cell lines. We have also observed that 17-alpha-estradiol (alpha-E2), a weak estrogen, shows neuroprotective efficacy in the SK-N-SH cell line at concentrations equivalent to beta-E2. Finally, we have observed that tamoxifen, a classic estrogen antagonist, blocks only one-third of the neuroprotective effects of either alpha-E2 or beta-E2. Collectively, these results indicate that estrogen is behaviorally active in tests of learning/ memory; activates basal forebrain cholinergic neurons and neurotrophin expression; and is neuroprotective for human neuronal cultures. We conclude that estrogen may be a useful therapy for AD and other neurodegenerative diseases.

Alzheimer Disease↗

PubMed1996

Effects of discrete kainic acid-induced hippocampal lesions on spatial and contextual learning and memory in rats.

Substantial information is available concerning the influence of global hippocampal lesions on spatial learning and memory, however the contributions of discrete subregions within the hippocampus to these functions is less well understood. The present investigation utilized kainic acid to bilaterally lesion specific areas of the rat hippocampus. These animals were subsequently tested on a spatial orientation task using a circular water maze, and on an associative/contextual task using passive avoidance conditioning. The results indicate that both the dorsal CA1 and the ventral CA3 subregions play important roles in learning. Specifically, CA1 lesions produced a deficit in the acquisition of the water maze task and a significant memory impairment on the passive avoidance task. CA3 lesions also caused learning deficits in the acquisition of the water maze task, and produced even greater impairments in performance on the passive avoidance task. We conclude that CA1 and CA3 hippocampal subregions each play significant roles in the overall integration of information concerning spatial and associative learning.

Animals↗

PubMed2003

Chronic neonatal N-methyl-D-aspartate receptor blockade induces learning deficits and transient hypoactivity in young rats.

A blockade of N-methyl-D-aspartate (NMDA)-type of glutamate receptor in rodents is believed to provide a pharmacological model of schizophrenia-related psychosis. Since neurodevelopmental abnormality, at least partly, could contribute to the pathogenesis of schizophrenia, the aim of this study was to recapitulate cognitive impairments accompanying this disorder in rats by a chronic neonatal treatment with a noncompetitive NMDA antagonist MK-801. Rat pups were treated with a low dose of MK-801 (0.05 mg/kg s.c.) chronically from early postnatal period (PD 7-49) known to be critical for glutamatergic system maturation. Locomotor activity in the "open-field" test, anxiety level in the elevated plus-maze test, and learning capacity in food rewarded spatial task were examined in young animals. Chronic MK-801 treatment produced a decrease of spontaneous motor and exploratory activity in 16- to 28-day-old rats. At the same time, a hyperlocomotion in response to acute administration of MK-801 was observed as well. Spatial learning of MK-801-treated rats was found to be negatively affected. Treated rats were able to respond to stress stimuli in the adequate manner but their anxiety level was found to be lower than in controls. Behavioral disturbances appeared to be temporary, and no such abnormalities could be detected at the age of 16 weeks. Thus, even mild chronic neonatal blockade of NMDA receptors may lead to a specific pattern of cognitive abnormalities presumably resulting from impairments of sensory information processing at the cortical-basal ganglia level.

Animals↗

PubMed2026

Individual Differences in Cognitive Aging Rodent Datasets (ID-CARD): A collaborative platform for behavioral analysis across the lifespan.

Understanding cognitive aging requires approaches that capture individual variability while enabling integration across studies. In rodent models, behavioral data are central to this effort, yet cross-laboratory differences in experimental design limit comparability and constrain secondary analysis. To address this gap, we developed the Individual Differences in Cognitive Aging Rodent Datasets (ID-CARD), a first-of-its-kind collaborative repository aggregating trial-level Morris water maze data from multiple laboratories. ID-CARD is designed to support large-scale, integrative analyses and to facilitate secondary use of existing behavioral data in alignment with emerging data-sharing and transparency initiatives. Rather than imposing retrospective harmonization of experimental protocols, we implemented a normalization and modeling framework that enables comparison of learning trajectories while preserving meaningful variation across studies. Behavioral data from > 5000 rats spanning common strains, both sexes, and multiple ages were normalized in training and performance domains and fit with a logarithmic function to derive an error accumulation rate coefficient (EARC) as a measure of spatial learning. Age was strongly associated with increased EARC, indicating attenuated learning, even after adjusting for non-spatial cue performance. Analyses of goodness of fit revealed systematic structure in learning dynamics, where age was associated with reduced learning-curve conformity after accounting for overall performance. Inter-individual variability in spatial learning also increased with age, with strain-specific interactions. These findings demonstrate that integrated analysis of heterogeneous behavioral datasets can yield robust, individual-level insights into cognitive aging. ID-CARD provides a scalable resource and analytic framework to advance discovery in behavioral neuroscience by enabling reuse, integration, and comparative analysis of existing data.

Cognitive aging↗

PubMed1993

Landmark stability is a prerequisite for spatial but not discrimination learning.

Neurons sensitive to both place and direction from distinct regions of the hippocampal formation, allometric relationships between spatial learning and hippocampal structure and pronounced impairments in spatial learning after lesions in this area, indicate that the hippocampal formation subserves allocentric spatial learning. To learn more about the process of spatial representation, we have developed a task that provides independent control of both landmark and directional cues. On the basis of physiological and behavioural work, this task also makes it possible to investigate the relevance of associative learning principles, such as predictability, to the spatial domain. We report here that although rats learn to discriminate between landmarks on the basis of their proximity to a reliably predicted food reward, they will only learn to use them to represent its location if they maintain stable locations within a geometric frame of reference.

Animals↗

PubMed2002

Chronic ethanol consumption induces tolerance to the spatial memory impairing effects of acute ethanol administration in rats.

A large number of studies in rats have investigated the effects of acute and chronic ethanol administration on performance on many spatial learning and memory tasks. However, no study has addressed the problem of whether chronic ethanol consumption induces tolerance to acute ethanol-induced spatial memory deficits. In this study, we analyzed the behavioral effects of acute ethanol administration on spatial memory and locomotor activity in rats chronically intoxicated by ethanol. Male Sprague-Dawley rats were given as their only available liquid source a 10% (v/v) aqueous ethanol solution for 2 weeks before behavioral testing and during the 1-week behavioral testing period. They were treated intraperitoneally with 1.5 g/kg of ethanol 30 min before daily training in the Morris water maze, a spatial memory task sensitive to hippocampal damage. Our results demonstrate that learning and spatial memory of ethanol-consuming animals were not altered compared with control rats. Chronic ethanol consumption had no effect on spatial reference memory in terms of either the distance traveled to find the hidden platform during the acquisition phase of the experiment, or the time spent in the training quadrant during the retention trial. Acute ethanol administration impaired spatial memory in control rats and this impairment was reversed in chronic ethanol-consuming animals, revealing that chronic ethanol consumption did induce tolerance to the spatial memory deficits induced by acute ethanol injection, although plasma ethanol levels did not differ between the two groups. In contrast, chronic ethanol consumption did not induce tolerance to the acute ethanol-induced stimulatory locomotor activity measured in the same animals. Our results, therefore, indicate that chronic ethanol consumption induces tolerance to the cognitive impairing effects, but not to the locomotor stimulatory effects of acute ethanol administration in rats, suggesting that these two behavioral effects of ethanol do not share a common mechanism in the CNS.

Alcohol Drinking↗