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PubMed1991

Paternal alcohol consumption in the rat impairs spatial learning performance in male offspring.

Pubescent (30 day old) male rats were maintained on an alcohol liquid diet containing 35% ethanol-derived calories (ALC) for 39 days or were pairfed an isocaloric control diet (PF). The concentration of alcohol in the diet was gradually increased to permit adaptation, then stabilized and then gradually tapered to prevent an alcohol withdrawal syndrome. Following a drug-free period (2 weeks), the males were mated with nontreated females. Offspring were evaluated on several developmental indices and on various learning/memory tasks to assess functional deficits in adulthood. Offspring sired by ALC-treated males did not differ from the offspring of PF males on several developmental parameters including body weights, when developmental landmarks appeared, or on tests of sensorimotor development. As adults, male offspring groups did not differ on tests of activity or on an object exploration/recognition task. However, male offspring of ALC-treated males demonstrated impaired acquisition performance (days and errors to criterion) on a win-shift spatial discrimination in an eight-arm radial maze and on a win-stay discrimination (days to criterion) conducted in a T-maze at a later age. The radial maze results were replicated in a subsequent experiment using different groups of rats.

Alcohol Drinking↗
PubMed1981

Recovery of visual-spatial learning and memory in chronic alcoholics.

Administered the Memory-for-Designs Test and a verbal and visuospatial paired associate learning test to separate groups of alcoholics (N = 32) 3 and 11 weeks abstinent from alcohol and to a matched control group (N = 16). Alcoholics were not impaired in verbal learning. Alcoholics 3 weeks abstinent performed significantly less well than controls on all nonverbal tasks and less well than 11-weeks alcoholics on one nonverbal measure. No significant differences were found between 11-week alcoholics and controls. The results suggest that some recovery of function may occur in alcoholics after 10 weeks of abstinence. The data also support the hypothesis of impaired right hemisphere in alcoholics.

Alcoholism↗
PubMed1988

Experience during suckling alters later spatial learning.

These experiments explore the role of preweaning experience in learning during the juvenile period. Pups that had been reared with many nipples available reached criterion on an 8-arm radial maze in a few trials; conversely, pups reared with only a few nipples required 3 times the number of trials to reach criterion (Experiment 1). Pups that had been reared with relatively few nipples available rarely nipple-shifted, while those that had been reared with a particularly high density of nipples shifted more frequently (Expt 2). A rearing procedure was devised that allowed precise experimental control of all phases of the suckling experience (Expt 3). Allowing or preventing a single behavior, nipple-shifting, while holding all other variables constant, was sufficient to affect acquisition of the maze task. In Experiment 4, the specificity of the early experience for later tasks was explored using a variety of nonspatial, lever-pressing operants. Rearing condition did not affect acquisition of a lever-pressing operant or of a visual discrimination task. However, pups reared with a high density of nipples responded at higher rates to a variable interval schedule and were more resistant to extinction. The possibility that strategy, rather than learning ability, was affected by rearing condition was assessed using a 2-arm maze task that was structured to present an optimal strategy of either win-shift or win-stay (Expt 5). The ease with which rats acquired the win-stay task was unaffected by rearing condition; all groups performed at about chance levels. However, pups reared with many nipples more readily acquired the win-shift task.

Animals↗
PubMed1992

Pharmacological dissociation between the spatial learning deficits produced by morphine and diazepam.

This study sought to determine whether the place learning deficits produced by diazepam are a secondary result of opioid release. Rats pretreated with diazepam (3 mg/kg) or morphine (15 mg/kg) were trained in the Morris water maze. Diazepam impaired place learning-slowing acquisition and preventing the formation of a quadrant preference. Morphine also slowed acquisition, but did not prevent place learning, and impaired escape to a visible platform. Flumazenil blocked the deficits produced by diazepam, but not morphine. Naloxone (2 mg/kg) blocked the deficits produced by morphine, but not diazepam. A high dose of naloxone (10 mg/kg) slowed acquisition, and exacerbated the deficit produced by diazepam. These results demonstrate that diazepam interferes with mnemonic processes through endogenous benzodiazepine receptors, independently of opioidergic systems. Further, they suggest that morphine interferes with motivational processes through opioidergic systems, independently of endogenous benzodiazepine systems.

Animals↗
PubMed1994

Methamphetamine exposure during early postnatal development in rats: I. Acoustic startle augmentation and spatial learning deficits.

Methamphetamine (MA) induces neurotransmitter reductions and neurotoxicity at high doses in adult animals, but its effects on early brain development and behavior have received less attention. In this experiment the effects of MA exposure during a period equivalent to the human third trimester were examined. Rats (Sprague-Dawley CD) were injected subcutaneously with d-MA (30 mg/kg b.i.d.) early in postnatal development (days 1-10), later (postnatal days 11-20), or with water during both of these periods. Both early and later MA-exposed offspring exhibited augmented acoustic startle and impaired performance in a complex multiple-T water maze. Only the early MA exposure group showed a persistent deficit in weight while only the later MA exposure group showed impaired learning in the Morris hidden platform maze. Effects on locomoter activity are reported in the accompanying article. It was concluded that the effects of MA are both long lasting and stage dependent and involve cognitive as well as arousal functions.

Acoustic Stimulation↗
PubMed1993

Chronic treatments with cholinoceptor drugs influence spatial learning in rats.

Nicotine, scopolamine, oxotremorine, diisopropyl-fluorophosphate (DFP) and tetrahydroaminoacridine (THA) were administered chronically to different groups of rats in doses reported to alter central muscarinic and/or nicotinic receptor numbers. Beginning 24 h after final drug injection, the groups were compared to a vehicle control group on acquisition of a hidden platform position in the Morris water maze over 20 trials with a 30-min inter-trial interval. Chronic treatment with either nicotine or scopolamine significantly improved the rate of learning, but oxotremorine and DFP retarded learning and THA had no effect on learning. The chronic drug effects on behaviour were consistent with known effects of the injected drugs on muscarinic and nicotinic binding in the forebrain and on the sensitivity of frontal cortex neurones to iontophoretically applied cholinoceptor agonists. However, alternative explanations for the observed changes cannot be ruled out, since the drugs used are known to have a wide range of effects on other neurotransmitters.

Animals↗
PubMed1993

The nootropic compound BMY-21502 improves spatial learning ability in brain injured rats.

Although long-lasting cognitive dysfunction often follows clinical traumatic brain injury (TBI), few pharmacologic regimens have been developed to treat post-traumatic cognitive deficits. We have previously shown that, in the rat, experimental lateral fluid-percussion (FP) brain injury induces a profound impairment in retrograde memory. In the present study, we characterized alterations in the ability of rats to learn a novel task following lateral FP brain injury and examined the potential modulatory effects of the nootropic cognitive enhancer BMY-21502 on post-injury learning. Male Sprague-Dawley rats were subjected to lateral (parasagittal) FP brain injury of moderate severity (2.4 atm) or sham surgery (no injury). On days 7 and 8 post-injury, animals were tested in a Morris water maze for their ability to learn to navigate to a submerged, invisible platform using external visual cues. BMY-21502 (10 mg/kg) or vehicle was administered 30 min prior to the first trial on both days. A highly significant (P < 0.001) impairment in post-injury learning was observed in vehicle-treated brain-injured animals compared with vehicle-treated sham animals. Injured animals treated with BMY-21502 at one week post-injury showed significantly (P < 0.05) improvement in post-injury learning ability compared to injured animals treated with vehicle. Paradoxically, in uninjured control animals BMY-21502 treatment appeared to worsen learning scores. The results of this study indicate that BMY-21502 may be useful for attenuating the dysfunction in learning ability that occurs following TBI.

Animals↗
PubMed1991

The effects of NGF and fetal cell transplants on spatial learning after intradentate administration of colchicine.

This study was performed to assess the effects of NGF infusion alone or in combination with fetal hippocampal transplants on recovery of function after damage to hippocampal dentate granule cells. Two groups of male Fischer-344 rats received bilateral infusions of colchicine (COLCH; 2.5 micrograms/site) or artificial cerebrospinal fluid (ACSF; 0.5 microliter) through chronic indwelling cannulae into the dentate gyrus. At the time of COLCH injection, a unilateral intracerebroventricular (ICV) cannula was implanted. One week later, when animals were tested in activity chambers for 60 min, COLCH-treated rats showed a significant increase in spontaneous locomotor activity. Two weeks after COLCH treatment, animals were assigned to various post-treatment groups and received 1.0 microliter of rat fetal hippocampal cell suspensions (ED-17 or 18) or Earle's basic salt solution in the same site as previous hippocampal infusions. Modified Alzet miniosmotic pumps (0.25 microliter/h) containing NGF (10 ng/microliter) or ACSF with cytochrome C (20 ng/microliter) were implanted subcutaneously and attached to the previously implanted ICV cannulae. The animals were tested for learning ability in a Morris water maze task starting 6 or 12 weeks post-COLCH. During both test periods, COLCH lesions significantly impaired acquisition and retention. At 6 weeks postlesion, NGF treatment ameliorated this COLCH-induced behavioral deficit while the presence of transplants did not ameliorate the COLCH-induced learning deficit. COLCH/transplant/NGF-treated rats performed better than both COLCH-lesioned rats with or without transplants. At 12 weeks postlesion COLCH-induced behavioral deficits were not ameliorated by NGF or transplants. Morphological examination performed after behavioral testing confirmed the presence of viable transplants and COLCH-induced granule cell loss. Exogenous NGF infusions appeared to have no effect on the morphological measures taken. These data demonstrate a time-dependent facilitative effect of exogenously applied NGF on functional deficiencies produced by experimentally induced neurodegeneration in the dentate gyrus of the hippocampus.

Animals↗
PubMed1989

A novel NMDA antagonist, MK-801, impairs performance in a hippocampal-dependent spatial learning task.

N-Methyl-d-aspartate (NMDA) receptors have been implicated with the triggering of long-term potentiation, a currently studied physiological model of learning and memory. The compound (+)-5-methyl-10,11-dihydro-5H-dibenzo [a,d] cyclohepten-5,10-imine maleate (MK-801) has recently been classified as a potent and selective NMDA antagonist acting at the associated ion channel. After determination of the highest intraperitoneal dose of MK-801 at which increases in activity (measured in photocell activity cages and 3-arm maze) were not observed (0.2 mg/kg), rats that had been previously trained to obtain food pellets in an 8-arm radial maze up to criterion were tested with 0.1 and 0.2 mg/kg doses. Dose-related decreases in "efficiency" in the task were found. The present findings support the suggestion that NMDA antagonists cause impairments in "working memory" and also support the status of long-term potentiation as a physiological model of memory.

Animals↗
PubMed1992

Effect of oxiracetam on scopolamine-induced amnesia in the rat in a spatial learning task.

The effects of the nootropic agent 4-hydroxy-2-oxopyrrolidinoacetamide (oxiracetam) on memory and performance impairments induced by scopolamine were evaluated in the Morris water maze task. No effect was seen on the performance of rats when treated with oxiracetam (30 mg/kg, IP) alone. Task performance of scopolamine (0.2 mg/kg, SC)-treated rats was impaired as compared to that of control animals. The behavioral deficits expressed in the task by scopolamine treatment were attenuated by the same dose of oxiracetam.

Animals↗
PubMed1994

Effect of DAU 6215, a novel 5-HT3 receptor antagonist, on scopolamine-induced amnesia in the rat in a spatial learning task.

The effects of different doses (1, 10, 30, and 100 micrograms/kg, IP) of a new 5-hydroxytryptamine3 (5-HT3) receptor antagonist, 3-alpha-tropanyl)1H-benzimidazolone-3-carboxamide chloride (DAU 6215), on memory and performance deficits induced by SC 0.2 mg/kg scopolamine were assessed in the Morris water maze task. No effect was observed on the performance of rats treated with DAU 6215 alone. The doses of 10 and 30 micrograms/kg DAU 6215 attenuated these scopolamine-induced behavioral deficits.

Amnesia↗
PubMed1990

The effects of dorsal noradrenergic bundle lesions on spatial learning, locomotor activity, and reaction to novelty.

The dorsal noradrenergic bundle (DNB) of male Wistar rats was lesioned bilaterally using intracerebral injections of 6-hydroxydopamine neurotoxin. Some of the rats were trained in a water maze using an "alternation" strategy, where the two positions of the hidden platform in the pool were changed between successive trials in the daily tests, and other rats in a water maze, where the temperature of the water was lowered to about 11 degrees C. The rats trained in the cold-water maze were also tested in open-field and saccharin neophobia tests. No differences were found between the two groups in learning of water maze tasks or in locomotor activity in the open-field tests. However, the saccharin neophobia test revealed an increased neophobia in the DNB-lesioned rats.

Animals↗
PubMed1990

The effects of forebrain ischaemia on spatial learning.

Rats were subjected to 15 min of forebrain ischaemia using the 4-vessel occlusion method. Following recovery they were trained using place navigation learning in a Morris water maze and forced choice rewarded alternation in a T-maze. Ischaemic rats were impaired in place navigation learning but the deficit was transient and there was no impairment of subsequent transfer test performance. Food-rewarded forced-choice alternation in a T-maze revealed a persistent impairment in ischaemic rats. The behavioural deficits were associated with neuropathological damage in the CA1 cell layer of the dorsal hippocampus with varying degrees of damage in layers CA2, CA3 and CA4. Granule cells in the dentate gyrus were not visibly affected. Variable amounts of lesion damage were found in the dorsolateral striatum. Ischaemic rats are therefore impaired on both place navigation and forced choice rewarded alternation, suggesting that ischaemic brain damage affects reference and working memory processes to different extents. Forced choice alternation may be the more sensitive method of assessing cognitive changes caused by forebrain ischaemia.

Animals↗
PubMed1993

Stimulus configuration, spatial learning, and hippocampal function.

Schmajuk and DiCarlo (Psychol. Rev., 99 (1992) 268-305) introduced a neural network, which utilizes a biologically plausible backpropagation procedure, to describe configural paradigms in classical conditioning. The model correctly describes many experimental results under the assumption that aspiration lesions of the hippocampus eliminate (a) the competition between simple and configural stimuli to gain association with the unconditioned stimulus and (b) the adjustment of initially random configural stimuli. The present study extends the network to describe place learning. Under the assumption that ibotenic acid lesions of the hippocampus only impair the adjustment of initially random configural stimuli, the model correctly shows that ibotenic acid lesions might spare a configural discrimination but impair place learning. In general, the results are taken to support a hippocampal role in the modulation of stimulus configuration.

Animals↗
PubMed1995

Long-term potentiation and glutamate release in the dentate gyrus: links to spatial learning.

Long-term potentiation (LTP) in the dentate gyrus of the anaesthetized rat is associated with a persistent increase in the concentration of glutamate in the extracellular compartment. At the in vitro level, this is mirrored by an increase in the ability of slices or synaptosomes from potentiated tissue to release glutamate in response to a depolarizing stimulus. In both cases, the activity-induced enhancement of glutamate release is dependent on the activation of the NMDA receptor. A similar increase in glutamate release in vitro is observed in the dentate gyrus prepared from rats trained in a variety of learning tasks, including classical conditioning and the Morris water maze. These results are consistent with the hypothesis that similar presynaptic mechanisms are engaged in LTP and learning.

Animals↗
PubMedDate not supplied

Spatial learning and memory in the radial maze: a longitudinal study in rats from 4 to 25 months of age.

This longitudinal study was designed to investigate whether previous experience may influence performances and strategies of rats tested in the radial maze without external cues when aged 4, 13, and 25 months. Their performances and strategies were compared with those of another group of rats tested only when aged 25 months. Expert old animals showed a good retention of previous experiences, whereas age-matched nonexpert animals exhibited some acquisition deficits. On the contrary, in the course of aging, the animals kept modifying their strategies independently of experience. In summary, we can conclude that previous experience is likely to influence performances of the aged rat but not the strategies adopted which are strictly age-dependent and independent of acquired experience.

Aging↗