Morris Maze Performance Research Articles

Evidence for Phosphorylation-Dependent, Dynamic, Regulation of mGlu5 and Homer2 in Expression of Cocaine Aversion in Mice.

Cocaine-induced changes in the expression of the glutamate-related scaffolding protein Homer2 influence this drug's psychostimulant and rewarding properties. In response to neuronal activity, Homer2 is phosphorylated on S117/S216 by calcium-calmodulin kinase IIα (CaMKIIα), which induces a rapid dissociation of mGlu5-Homer2 scaffolds. Herein, we examined the requirement for Homer2 phosphorylation in cocaine-induced changes in mGlu5-Homer2 coupling, to include behavioral sensitivity to cocaine. For this, mice with alanine point mutations at (S117/216)-Homer2 (Homer2AA/AA ) were generated, and we determined their affective, cognitive and sensorimotor phenotypes, as well as cocaine-induced changes in conditioned reward and motor hyperactivity. The Homer2AA/AA mutation prevented activity-dependent phosphorylation of S216 Homer2 in cortical neurons, but Homer2AA/AA mice did not differ from wild-type (WT) controls with respect to Morris maze performance, acoustic startle, spontaneous or cocaine-induced locomotion. Homer2AA/AA mice exhibited signs of hypoanxiety similar to the phenotype of transgenic mice with a deficit in signal-regulated mGluR5 phosphorylation (Grm5AA/AA ). However, opposite of Grm5AA/AA mice, Homer2AA/AA mice were less sensitive to the aversive properties of high-dose cocaine under both place-conditioning and taste-conditioning procedures. Acute injection with cocaine caused dissociation of mGluR5 and Homer2 in striatal lysates from WT, but not Homer2AA/AA mice, suggesting a molecular basis for the deficit in cocaine aversion. These findings indicate that CaMKIIα-dependent phosphorylation of Homer2 gates the negative motivational valence of high-dose cocaine via regulation of mGlu5 binding, furthering an important role for dynamic changes in mGlu5-Homer interactions in addiction vulnerability.

Effects of high fat diet on Morris maze performance, oxidative stress, and inflammation in rats: Contributions of maternal diet

This study was undertaken to investigate the effects of prenatal and postnatal exposure to high fat diet on the brain. Female rats were divided into high fat diet (HFD) and control diet (CD) groups 4 weeks prior to breeding and throughout gestation and lactation. After weaning, male progeny were placed on a chow diet until 8 weeks old, and then segregated into HFD or CD groups. At 20 weeks old, rats were evaluated in the Morris water maze, and markers of oxidative stress and inflammation were documented in the brain. In comparison to rats fed CD, cognitive decline in HFD progeny from HFD dams manifested as a decline in retention, but not acquisition, in the water maze. HFD was also associated with significant increases in 3-nitrotyrosine, inducible nitric oxide synthase, IL-6, and glial markers Iba-1 and GFAP, with the largest increases frequently observed in HFD animals born to HFD dams. Thus, these data collectively suggest that HFD increases oxidative and inflammatory signaling in the brain, and further indicate that maternal HFD consumption might sensitize offspring to the detrimental effects of HFD.

Effects of neonatal (+)-methamphetamine on path integration and spatial learning in rats: effects of dose and rearing conditions

Postnatal day (P)11–20 (+)-methamphetamine (MA) treatment impairs spatial learning and reference memory in the Morris water maze, but has marginal effects on learning in a labyrinthine maze. A subsequent experiment showed that MA treatment on P11–15, but not P16–20, is sufficient to induce Morris maze deficits. Here we tested the effects of P11–15 MA treatment under two different rearing conditions on Morris maze performance and path integration learning in the Cincinnati water maze in which distal cues were unavailable by using infrared illumination. Littermates were treated with 0, 10, 15, 20, or 25mg/kg MA×4/day (2h intervals). Half the litters were reared under standard housing conditions and half under partial enrichment by adding stainless steel enclosures. All MA groups showed impaired Cincinnati water maze performance with no significant effects of rearing condition. In the Morris maze, the MA-25 group showed impaired spatial acquisition, reversal, and small platform learning. Enrichment significantly improved Morris maze acquisition in all groups but did not interact with treatment. The male MA-25 group was also impaired on probe trial performance after acquisition and on small platform trials. A narrow window of MA treatment (P11–15) induces impaired path integration learning irrespective of dose within the range tested but impairments in spatial learning are dependent on dose. The results demonstrate that a narrower exposure window (5 days) changes the long-term effects of MA treatment compared to longer exposures (10 days).

Voluntary exercise influences behavioral development in rats exposed to alcohol during the neonatal brain growth spurt.

Children exposed to alcohol prenatally may suffer from severe brain damage, expressed as a variety of behavioral problems, including hyperactivity and learning deficits. There is a critical need to identify effective treatments for fetal alcohol effects. Physical exercise enhances cognitive ability and increases neurogenesis in the hippocampus, a brain area important for learning and memory. Thus, the present study examined whether physical exercise might reduce the severity of alcohol-induced behavioral alterations. Sprague-Dawley rats were intubated with 5.25 g/kg/day ethanol during the third trimester equivalent (postnatal days [PDs] 4-9). Intubated sham control and nontreated controls were included. From PD 21 to PD 51, half of the subjects were given access to running wheels. On PD 52, subjects were tested on the Morris water maze, and on PD 60, open field activity levels were measured. Morris maze performance was significantly impaired among ethanol-exposed subjects; exercise significantly improved performance of all groups. Similarly, ethanol-exposed subjects were overactive in the open field, an effect attenuated with exercise. In sum, these data suggest that exercise may increase neuronal plasticity not only in controls, but also in subjects exposed to alcohol during development.

Effects of intraperitoneal lipopolysaccharide on Morris maze performance in year-old and 2-month-old female C57BL/6J mice

Several studies have shown that systemic lipopolysaccharide (LPS) or interleukin-1β (IL-1β) may affect performance in various learning tasks, including the Morris water maze. In the current study, female C57BL/6J mice, either 2 months or 1 year of age, were given 5 days of testing followed by 3 days of rest, and then three additional days of testing. Mice either received a single LPS injection on day 1 and saline on days 2–5, LPS injections on days 1–5, or saline injections on days 1–5. Daily LPS administration significantly prolonged latency for the animals to find the platform, and decreased their swimming speed. Year-old mice treated with LPS each day also exhibited significantly higher levels of thigmotaxis in the maze. Despite effects on latency and swim speed, no effect of LPS treatment was observed for distance traveled to the platform or other measures that clearly indicate disruption of learning in the maze. On the other hand, age was a significant factor affecting both latency and distance, with older animals swimming greater distances to find the platform. Additionally, older animals were more adversely affected by daily LPS treatment. In this study, although LPS-induced performance impairments in the Morris water maze were noted, particularly in older animals, these effects were not clearly indicative of learning impairment per se.

Developmental D-methamphetamine treatment selectively induces spatial navigation impairments in reference memory in the Morris water maze while sparing working memory.

In previous studies, we have shown that P11-20 treatment with D-methamphetamine (MA) (10 mg/kg x 4/day at 2-h intervals) induces impairments in spatial learning and memory in the Morris water maze after the offspring reach adulthood. Using a split-litter, multiple dose, design (0, 5, 10, and 15 mg/kg MA administered s.c. 4/day at 2-h intervals), the spatial learning effect was further explored with a multiple shifted platform (reversal), reference memory-based procedure and a working memory procedure. Prior to spatial learning, animals were first tested for swimming ability (in a straight swimming channel), sequential learning (in the Cincinnati multiple-T water maze), and proximal cue learning (in the Morris water maze). Rats were then assessed in the hidden platform, reference memory-based spatial version of the Morris maze for acquisition and on five subsequent phases in which the platform was moved to new locations. After the reference memory-based, fixed platform position learning phases, animals were tested in the trial-dependent, matching-to-sample, working memory version of the Morris maze. No group differences were found in straight channel, sequential maze, or cued Morris maze performance. By contrast, all MA groups were impaired in spatial learning during acquisition, multiple shift, and shifted with a reduced platform phases of reference memory-based learning. In addition, MA animals were impaired on memory (probe) trials during the acquisition and shifted with a reduced platform phases of learning. No effects on trial-dependent, matching-to-sample, working memory were found. The findings demonstrate that neonatal treatment with MA induces a selective impairment of reference memory-based spatial learning while sparing sequential, cued, and working memory-based learning.

Angiotensin converting enzyme inhibition partially prevents deficits in water maze performance, hippocampal synaptic plasticity and cerebral blood flow in streptozotocin-diabetic rats

Vascular dysfunction is important in the pathogenesis of peripheral complications of diabetes. However, the effects of diabetes on cerebral blood flow and the role of vascular deficits in the pathogenesis of diabetic encephalopathy are still unknown. The present study examined whether experimental diabetes is associated with reduced cerebral blood flow and whether treatment with enalapril can improve cerebral perfusion and function (blood flow and functional cerebral deficits). Streptozotocin-diabetic rats were treated with the ACE inhibitor enalapril (24 mg/kg) from onset of diabetes. After 14 weeks of diabetes, 12 enalapril treated and 12 untreated diabetic rats, and 12 nondiabetic age-matched control rats were tested in a spatial version of the Morris water maze. After 16 weeks of diabetes, in the same groups, blood flow in the hippocampus and thalamus was measured by hydrogen clearance microelectrode polarography. In a separate study, hippocampal long-term potentiation was measured after 26 weeks of diabetes. Water maze performance and hippocampal long-term potentiation were impaired in diabetic rats. Furthermore, blood flow in diabetic rats was reduced by 30% ( P<0.001) in the hippocampus and by 37% ( P<0.005) in the thalamus compared to nondiabetic controls. Enalapril treatment significantly improved water maze performance ( P<0.05), hippocampal long term potentiation ( P<0.05) and hippocampal blood flow ( P<0.05). Cerebral perfusion is reduced in diabetic rats compared to controls. Treatment aimed at the vasculature can improve cerebral blood flow, deficits in Morris maze performance and long term potentiation. These findings suggest that vasculopathy plays a role in the development of cerebral dysfunction in diabetic rats.

Progressive age-related impairment of cognitive behavior in APP23 transgenic mice

Transgenic APP23 mice expressing human APP 751 with the K670N/M671L mutation, were compared at ages 3, 18 or 25 months to non-transgenic littermates in passive avoidance and in a small and large Morris maze. The task in the smaller pool habituated their flight response to the platform. Impairments in passive avoidance and small pool performance in APP23 mice were clearly age-related. In the larger Morris maze APP23 mice at all ages were impaired in latency and distance swum before finding the platform. Identical performance of 18-month APP23 and controls in a visible platform condition indicates that the Morris maze performance deficit was not due to sensory, motor or motivational alterations. At age 3 months both groups initially unexpectedly avoided the visible platform, suggesting that in young mice neophobia may contribute significantly to performance in cognitive tests. In conclusion, APP23 mice exhibit both early behavioral impairment in the large Morris maze as well as impairments in passive avoidance and small pool performance that are marked only in old age.

Effects of the size of the Morris water tank on spatial discrimination learning in the CFW1 mouse

The spatial orientation of mice and rats in tasks such as the Morris water escape task is guided by extramaze cues. Using data from the control groups of mice used in two drug-finding experiments, we addressed the question whether the size of the Morris water tank affects spatial learning in mice. In these experiments, CFW1 mice had been tested in either a small or a large water tank. Reanalysis of the data revealed that pool size did not affect learning or bias for the previous training quadrant. The Morris water escape task appears to act as a severe stressor in particular mouse strains, and a high stress level may interfere with the learning ability or performance of mice, which may have serious consequences for the interpretation of data. This is of special relevance when assessing the Morris maze performance of strains of mice with a different sensitivity to stress. We conclude that mice can best be tested in a small pool, because the time and distance swum to find and escape onto the platform is decreased and the probability of success (that is, of encountering the platform) is increased. This will reduce stress and hence increase the comparability of data between different strains of mice.

Cerebral hypoperfusion yields capillary damage in the hippocampal CA1 area that correlates with spatial memory impairment

The impact of chronic cerebral hypoperfusion on cognitive function and cerebral capillary morphology in the hippocampus was examined. Young adult Wistar rats were subjected to permanent ligation of both common carotid arteries (two-vessel occlusion). One month after vascular occlusion, a small but non-significant impairment in the acquisition of spatial information was registered compared with sham-operated controls. Two months after surgery, the occluded animals displayed an impaired performance throughout the training period. One year after surgery, the acquisition curves demonstrated a significant attenuation of the learning rate in the occluded rats group, whereas no significant differences in long-term retention were observed. Thus, chronic hypoperfusion induced by two-vessel occlusion gave rise to impairment of spatial memory. Following behavioural testing, the rats were killed at the age of 17 months, and capillaries in the CA1 and dentate gyrus were examined using transmission electron microscopy. Typical age-related capillary abnormalities such as degenerative pericytes and thickened basement membranes (with or without fibrosis) were detected in the hippocampus of sham animals. In occluded rats, the occurrence of capillaries displaying such abnormalities almost doubled in the CA1 region, but was similar in the dentate gyrus, compared with sham controls. A highly significant correlation was found between the last Morris maze performance and the percentage of capillaries with deposits in the basement membrane in the hippocampal CA1 area of occluded rats, which was not present in the sham animals. We conclude that a long-term hypoperfusion accelerated the development of age-related ultrastructural aberrations of capillaries in the hippocampal CA1 area, but not in the dentate gyrus. Thus, not only neurons, but also capillaries in the hippocampal CA1 area are sensitive to an impaired microcirculation. Moreover, the cognitive performance of hypoperfused rats correlated closely with the condition of the capillaries in the CA1 area, suggesting that capillary integrity is one of the important determinants of brain function in conditions that compromise cerebral microcirculation.

The Effects of Early Environment on the Development of Functional Laterality in Morris Maze Performance

The current study examined the contribution of early postnatal experience to the functional lateralisation of spatial ability in the male rat. Litters were handled (H) or non-handled (NH) during the first 20 days of life, and three males from each litter were tested in the Morris water maze in adulthood. Two subjects from each litter were monocularly tested, one with the right eye patched and the other with the left eye patched. A third subject in each litter was tested with both eyes open. Handling interacted with Eye Patch for time and distance measures. Performance of Right- and Left-Patched rats was equivalent for the NH group, but the H subjects tested with the Right Patch outperformed H subjects with the Left Patch. These results confirm studies that found spatial navigation performance to be lateralised to the right hemisphere in male rats. The data indicate that functional asymmetry of spatial navigation behaviour in the adult male rat is sensitive to environmental influences during early development.

The Effects of Early Environment on the Development of Functional Laterality in Morris Maze Performance

The Effects of Early Environment on the Development of Functional Laterality in Morris Maze Performance

Postoperative Environmental Enrichment Attenuates Fimbria-Fornix Lesion-Induced Impairments in Morris Maze Performance

Male Wistar rats were given a bilateral or a unilateral transection of the fimbria-fornix; subsequently they were kept in standard laboratory housing conditions or in enriched environments for 6 weeks, after which they were tested in the Morris maze. In the acquisition phase of the experiment rats with a bilateral lesion of the fimbria-fornix were markedly impaired in their ability to locate the hidden platform, while rats with unilateral lesions displayed no such impairment. However, rats with a bilateral lesion displayed a less severe deficit when they had been housed postoperatively in the enriched environment. In the retention phase of the experiment rats with a bilateral lesion swam markedly less time in the platform zone only when they had been housed in standard conditions. They also spent more time in the edge zone than the other groups. Rats with a bilateral lesion that were housed enriched did not swim more in the edge zone. Despite their good performance during acquisition they did not display a clear preference for the platform zone. Thus, it was speculated that enriched rats with a bilateral lesion had learned to leave the side of the pool to search for the platform and with the aid of this different strategy improved their performance.

Learning impairment in transgenic mice with central overexpression of corticotropin-releasing factor

The present studies were designed to test the learning and memory capacities of transgenic mice with central overexpression of corticotropin-releasing factor in a forced alternation water T-maze task and in the Morris water maze. In T-maze testing, littermate control mice reached a criterion of 70% correct responses after five days of trials, while the performance of transgenic subjects was still random after the same training. In Morris maze testing, control subjects reached the submerged platform significantly faster [ F (1,48) = 4.51, P < 0.05] after three days of trials, while the performance of transgenic mice was unimproved over the same period. The deficit in Morris maze performance in transgenic mice was reversed when the platform was visible above the surface of the water. Pre-test administration of the benzodiazepine anxiolytic, chlordiazepoxide (10 mg/kg), before acquisition training also produced a significant [ F (4,40) = 16.61, P < 0.001] and persistent improvement in Morris maze performance in transgenic mice when compared to vehicle-treated transgenic litter mates. Finally, there was no evidence of hippocampal cell loss in transgenic brains. These results suggest that corticotropin-releasing factor- overexpressing mice subjects exhibit a profound learning deficit without sensory or motor-related impairments, and that memory plasticity can be restored by anxiolytic pre-treatment. Thus, constitutive overabundance of brain corticotropin-releasing factor may produce hyperemotionality that interferes with learned behaviors. Stress-related disorders characterized by co-morbid deficits in learning/memory may benefit from pharmacological normalization of brain corticotropin-releasing factor systems.

Long-term impoverished housing effects on morris maze performance after a fimbria lesion

Male Wistar rats received bilateral Fimbria lesions and were postoperatively housed in either standard social conditions or in impoverished conditions (one rat per cage) for 2 weeks in experiment I, and for 7 months in experiment II. The effects of lesion and housing conditions were investigated in the Morris maze spatial orientation task. Fimbria lesions increased the latency to reach the platform during acquisition in both experiments, which indicates that functional recovery of the Morris maze impairment does not occur in 7 months time. Post-operative impoverishment for 2 weeks or for 7 months reduced the lesion induced deficit in Morris maze acquisition, while it had a more general effect in the trial without platform. Interestingly, the impoverishment effects were not more severe after 7 months, but even less easily detected. These findings are interpreted as if impoverishment affects the reactiveness of animals to external stimuli, which may help the animal to compensate for the lesion-induced-deficit in Morris maze learning.

Acute and longer term effects of meso-2,3 dimercaptosuccinic acid (DMSA) on the behavior of lead-exposed and control mice

We investigated the effect of chelating agent meso-2,3 dimercaptosuccinic acid (DMSA_ on spatial learning and forced-swim immobility in Binghamton Heterogeneous Stock (HET) mice. Forced-swim immobility (characterized by increasingly frequent bouts of complete motionlessness in a forced-swim test, i.e., behavioral despair) is reduced by exposure to lead. In Experiment 1, male and female HETs ( n = 81) were assigned to lead-exposed (0.5% lead acetate ad lib in drinking fluid), pair-fed (PF), or water control groups. Six weeks after the termination of lead exposure, half of each group was injected intraperitoneally (IP) with 50 mg/kg DMSA or vehicle once per day for 5 days. Following treatment, all animals were tested for acquisition and extinction in the Morris Water maze, followed by immobility testing in an inescapable forced-swim task. Neither Pb nor DMSA affected Morris maze performance. However, consistent with previously published work, Pb reduced immobility in the forced-water swim relative to both PF and water controls. Additionally, lead-exposed males, but not females, showed sustained improvement following DMSA treatment on immobility measures. Experiment 2 was designed to demonstrate the effect of the above DMSA protocol on blood-Pb, and also examined the immediate effects of DMSA on immobility during treatment. Thus, in Experiment 2, animals were exposed to an identical Pb and DMSA treatment protocol, but the effects of DMSA on immobility during the course of DMSA treatment were measured, and animals were sacrificed immediately after treatment so that blood-Pb measures could be taken. Under these circumstances, DMSA markedly reversed the lead-induced reduction in immobility immediately during the treatment phase. Although DMSA clearly reduced blood-lead in males, its influence on female blood levels was far less. Taken together, the data from these experiments suggest that DMSA ameliorates lead-induced immobility changes in mice, but that gender may modulate DMSA's effect on blood-lead and longer-term behavioral effects. However, further work is needed to clarify the role of gender in response to DMSA.

ACTH(4–9) analog ORG2766 treatment 7 months delayed still improves Morris maze performance of fimbria-lesioned rats

The ACTH(4–9) analog ORG2766 has been known to affect recovery of damaged functions resulting from injury to neural tissue. The peptides efficacy has often been ascribed to a facilitation of existing recovery, and immediate treatment seemed a prerequisite for efficacy. However, various results in other recovery paradigms do not refer to the neurotrophic properties of the peptide, but rather ascribe the effectiveness of ORG2766 to a general change in attention that indirectly affects functional recovery. Such a change in state is theoretically independent of the occurrence of spontaneous recovery, and, thus, treatment would not be required to coincide with recovery immediately after the damage. To see if ORG2766 can influence the recovery of function without the simultaneous occurrence of spontaneous recovery, this study employed a delay of 7 months after the occurrence of a fimbria lesion before ORG2766 was administered. The selective fimbria lesion produced an impairment in Morris maze performance, which could be attenuated by chronic treatment with ORG2766 immediately after the lesion as well as after 7 months. With respect to spatial orientation, no improvement is assessed in untreated lesioned rats, as the impairment of Morris maze performance in untreated fimbrialesioned rats is as severe as right after the lesion. The data indicates that efficacy of the ACTH(4–9) analog does not rely on the acceleration of spontaneous recovery processes in this paradigm. The behavioral effects of ORG2766 are discussed in the context of a peptide-induced state of enhanced attention.

Olfactory bulbectomy temporarily impairs Morris maze performance: An ACTH(4–9) analog accellerates return of function

Rats with a bilateral lesion of the olfactory bulb are permanently anosmic. However, this lesion also produces nonspecific behavioral effects that recover over time. In this study olfactory bulb-lesioned animals are given a spatial orientation task—the Morris maze—which supposedly relies on visual and not olfactory cues. In exp. 1 this assumption was verified by subjecting animals with peripherally induced anosmia to the Morris maze (olfactory neurons in the nasal mucosae were destroyed by flushing the nose with ZnSO4). Anosmia did not affect the acquisition rate of the animals. In exp. 2 anosmia was produced by a central lesion to the bulbus olfactorius. Two weeks after lesioning the Morris maze performance is severely impaired. Interestingly, chronic administration (10μg/48 h/rat, during these 14 days, SC) of the ACTH(4–9) analog ORG 2766 diminished the impairment in performance. In exp. 3 olfactory bulb-lesioned animals were allowed 6 wk to recover before Morris maze testing began, to investigate if spontaneous recovery of performance occurred. No difference was seen in the acquisition performance of lesioned animals when compared to sham animals at this timepoint. The effect of the peptide is discussed in the context of an accelleration of the recovery of nonspecific consequences of brain lesioning.

Selective reduction of hippocampal dentate frequency potentiation in aged rats with impaired place learning

Induction of posttetanic potentiation (PTP) and long-term potentiation (LTP) was analyzed in hippocampal slices obtained from a) young 6-month-old Sprague-Dawley (SD) rats, all of them performing well in the Morris Maze, and b) aged SD 20-month-old and Fischer 344 24-month-old rats showing different degrees of ability in the same test. After the application of an electrical tetanus 1 s, 100 Hz, 50 μA in the stratum radiatum, no significant differences were found in the percent of induction of both PTP and LTP in the CA1 area of hippocampal slices obtained from rats of different strains and ages. After the application of an electrical tetanus 1 s, 100 Hz, 50 μA in the stratum moleculare, a significant difference was found in the percent of dentate PTP induction in hippocampal slices obtained from rats of different ages. Specifically, dentate PTP induction was significantly ( p < 0.01) higher in slices obtained from young SD rats, and from old SD rats with a better performance in the Morris maze, escape latency less than 10 s and 150 cm, than in slices obtained from old SD or Fischer 344 rats that had shown poor performance in the Morris Maze. On the contrary, no significant differences were found in the percent of dentate LTP in hippocampal slices obtained from rats of different strains and ages. The data demonstrate that the induction of hippocampal dentate high-frequency PTP is selectively reduced in old rats with impaired Morris Maze performance.

Scopolamine does not differentially affect Morris maze performance in adult rats exposed prenatally to alcohol

Rats exposed prenatally to alcohol have shown deficits in spatial learning in radial-arm and Morris mazes. Prenatal exposure to alcohol in rats has also been shown to alter central nervous system (CNS) cholinergic function. Since cholinergic dysfunction disrupts spatial learning in normal rats, the present experiment assessed the role of putative prenatal alcohol-induced cholinergic dysfunction in spatial learning in rats. Pregnant rats were fed alcohol via liquid diet from gestation day 6 to 20. Control dams were pair-fed liquid diet without alcohol or fed ad lib lab chow and water. Group housed adult male and female offspring (postnatal days 110 to 135) were given scopolamine-HCl (o, 0.5, or 1.0 mg/kg/day) and tested in a Morris maze, with four trials per day for four days. A 15-s probe trial preceded testing on days 2–4. On day 5, the rats were given four trials to learn a new platform location. Scopolamine produced dose-dependent increases in latency to find the platform for all groups. There were no significant differences among prenatal treatment groups in scopolamine-induced shifts in performance. The results did not support the hypothesis that prenatal alcohol-induced CNS cholinergic dysfunction is related to spatial learning performance in these rats.