A differential involvement of the shell and core subterritories of the nucleus accumbens of the rats in memory processes.

The role of the core and the shell subterritories of the nucleus accumbens in conditioned freezing and spatial learning was investigated by means of selective N-methyl-D-aspartate lesions. Shell-lesioned rats showed reduced conditioned freezing to context and a tendency toward reduced freezing to the discrete stimulus compared with controls. However, lesions of the core did not modify the freezing response either to the context or to the discrete stimuli. Although spatial memory, as assessed by a water-maze paradigm, was not disrupted by the lesions, in a 4-arm baited, 4-arm unbaited radial-arm maze paradigm, the shell-lesioned rats showed selective deficits in working memory, but not in reference memory. In contrast, core-lesioned rats showed no memory deficits. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

The effects of cytotoxic perirhinal cortex lesions on spatial learning by rats: A comparison of the dark Agouti and Sprague-Dawley strains.

The effects of perirhinal cortex lesions in rats on spatial memory might depend on the choice of strain. The present study, therefore, compared perirhinal lesions in Sprague-Dawley rats (associated with deficits) with Dark Agouti rats (associated with null effects). Tests of reference memory and working memory in the water maze failed to provide evidence that perirhinal lesions disrupt overall levels of performance (irrespective of strain) or that these lesions have differential effects on the rates of spatial learning in these 2 strains. Strain differences were, however, found, as the Dark Agouti strain was often superior. Furthermore, the perirhinal lesions did have differential effects in the 2 strains, but these did not appear to relate directly to changes in spatial learning. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

p-ANCA target antigens in ulcerative colitis

Isolated hearts from two strains of rats bred for sensitivity or resistance to amygdala kindling that also exhibit, in vivo, differential sensitivity to the cardiotoxicity of cocaine were studied. The goal was to determine if the differential cardiotoxic sensitivity was due, at least in part, to intrinsic strain-dependent differences in the heart. The Langendorff preparation was used (n=8 per strain). Hearts were perfused with increasing concentrations of cocaine (5 x 10(-6), 1 x 10(-5), 5 x 10(-5), 1 x 10(-4), and 5 x 10(-4) M) for 5 min with a 5 min washout between exposure to successive concentrations. Consistent with in vivo observations, hearts from genetically slow amygdala kindling rats (Slow) required lower cocaine doses to develop cardiac arrhythmias and arrest as compared to the hearts from genetically fast amygdala kindling rats (Fast). At 5 x 10(-5) M cocaine arrhythmias occurred in 38% (3/8) Slow and 0% Fast hearts. Five of 8 Slow hearts and none of 8 Fast hearts were arrested by 10(-4) M cocaine. Arrest in Fast hearts occurred only with 5 x 10(-4) M cocaine. Cocaine constricted coronary arteries (no significant difference between strains). On the other hand, coronary arteries of Slow but not Fast hearts dilated during cocaine washout after perfusion with all but the highest concentration of cocaine. We conclude that factors intrinsic to the heart and coronary artery influence the sensitivity or response of these structures to cocaine.     

Caloric restriction alters seizure disposition and behavioral profiles in seizure-prone (fast) versus seizure-resistant (slow) rats.

Caloric restriction (CR), primarily known for extending life span, has proven anticonvulsant in several seizure models and antiepileptogenic in a strain of inherently seizure susceptible mice. Our animal model consisted of a seizure-prone (Fast) strain that naturally exhibits attention-deficit/hyperactivity disorder (ADHD)-like behaviors and a comparison seizure-resistant (Slow) strain; we evaluated CR’s effect on the typical seizure sensitivities and behavioral profiles of each strain. Fast and Slow rats were fed ad libitum or were calorically restricted to 80% of free-feeding body weight. Rats were then tested in the open field (hyperactivity), Morris water maze (learning and attention), and restraint (impulsivity) paradigms and finally kindled from the amygdala. Ultimately, CR abolished signs of abnormal hyperactivity in the Fast strain and retarded their kindling rates, making it the first manipulation to demonstrate an antiepileptogenic effect in this animal model. CR also shortened seizure durations in fully kindled Slow rats but had no effect on their kindling rates, implying a differential effect of CR on genotype. These results clearly endorse further investigation into the potential benefits of CR for both epilepsy and ADHD. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Long-term study of chronic oral aluminum exposure and spatial working memory in rats.

The authors report an effort to advance animal models that mimic the cognitive decline of Alzheimer's disease. Rats were trained and repeatedly tested in a spatial delayed matching-to-position paradigm in the water maze, with the location of the submerged platform changing between, but not within, days. After Trial 1 (random search) and intertrial intervals of 30 s or 1 hr, memory was tested in Trial 2. Young rats quickly acquired this task and were repeatedly tested after different intervals over 7 months, with a slight increase in performance toward the end of testing, but no difference in latencies between delays. Oral long-term treatment of 1 group with 0.1 % aluminum caused no delay-dependent working memory deficit. This testing protocol may enable between- and within-subject long-term assessment of spatial working memory before and after drug treatment and may prove useful in animal models of progressive cognitive decline. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Low levels of estradiol facilitate, whereas high levels of estradiol impair, working memory performance on the radial arm maze.

Previous investigations of estradiol's effects on learning and memory yielded equivocal results. This study was designed to determine whether these inconsistencies were due to dose-dependent effects of estradiol on different memory processes. Ovariectomized female rats were injected daily with estradiol benzoate (EB; 0.32, 1.00, or 5.00 μg) or vehicle. Approximately 3 hr after injection, rats were run on a hippocampus-dependent working/reference memory version of the radial arm maze. Total number of working (WME), reference, and combined working/reference memory errors were scored. Compared with vehicle, 1.00 or 5.00 μg EB (high physiological) impaired performance by increasing the number of WME, whereas 0.32 μg EB (low physiological) facilitated performance by decreasing the number of WME. Taken together, these data demonstrate a dose-dependent effect of EB on working memory. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Perirhinal Cortex and Anterior Thalamic Lesions: Comparative Effects on Learning and Memory.

Three learning and memory tasks were used to compare the effects of neurotoxic anterior thalamic nuclei (ATN) and perirhinal cortex (PRC) lesions in rats. Rats with ATN lesions showed impaired spatial memory in a 12-arm radial maze, whereas rats with PRC lesions showed intact spatial memory, despite the use of minimal pretraining and extensive within-session delays (to 40 rain). PRC, but not ATN, lesions produced impairments on a configural learning task using complex visual-tactile cues in the radial maze. Neither ATN nor PRC lesions consistently affected spontaneous object recognition across extended sample-test delays (to 40 min). These findings confirm the differential involvement of the ATN and PRC in learning and memory. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Differences in kindling development in seven outbred and inbred rat strains

The kindling phenomenon, i.e., the progressive development of focal and secondarily generalized seizures upon repeated electrical stimulation of a limbic brain region, occurs in various species, but with marked differences in kindling rate between species and also within the same species. In rats, differences in kindling rates have been reported within the same strain and between different strains, and both genetic and environmental influences are thought to be involved in this variability. In most studies on kindling in rats, outbred strains such as Sprague-Dawley have been used. In the present study, we compared rates of amygdala kindling development in two outbred (Sprague-Dawley, Wistar) and five inbred (Lewis, Fischer 344, ACI, Wistar-Kyoto, Brown Norway) rat strains, including several strains which have not been kindled before. We were particularly interested which parts of the stepwise progression of kindling differ among these strains. Furthermore, the sensitivity of the basolateral amygdala to electrical stimulation was determined before and after kindling. Once daily electrical stimulation of the basolateral amygdala resulted in marked interstrain differences in kindling rates, with Sprague-Dawley and Brown-Norway rats exhibiting the lowest number of stimulations to reach fully kindled (stage 5) seizures, and Lewis rats showing the highest number of the 7 strains. In contrast to the significant differences in number of stimulations to reach the fully kindled state, total (cumulative) afterdischarge duration (ADD) to reach stage 5 did not significantly differ among strains, substantiating that cumulative AD is the principal factor in the acquisition of kindled seizures. Marked differences in ADD of a stage 5 seizure were obtained between strains, with strains kindling rapidly exhibiting longer ADD than strains kindling slowly. Postkindling afterdischarge threshold (ADT) varied significantly among strains, but only 3 of the 7 strains showed a decrease of ADT compared to prekindling values. When the stepwise progression of kindling was evaluated, pronounced interstrain differences were determined in the time spent in the initial phase of kindling, i.e., stage 1 seizures, both in terms of stimulations and cumulative ADD, indicating that variations in kindling rates were predominantly due to the time needed to progress from stage 1 to subsequent stages of the kindling process. The data seem to indicate that inbred rat strains offer an interesting resource for dissecting the underlying genetic basis for phenotypic differences in epileptogenesis as induced by kindling, although the high variability of kindling rates seen within some inbred strains weakens this possibility.     

Differential involvement of nucleus accumbens shell and core subregions in maternal memory in postpartum female rats.

Maternal memory refers to the long-term retention of maternal responsiveness as a consequence of animals' prior experiences with their young. This study examined the relative roles of 2 subregions of the nucleus accumbens (NA; shell and core) in maternal memory in rats. NA shell lesions either before or immediately after a short experience significantly disrupted maternal memory, but lesions after a 24-hr maternal experience had no effect. NA core lesions had no significant impact on maternal memory. Cycloheximide (a protein synthesis inhibitor) at a high dose (25 μg/μl) infused in the NA shell immediately after 1 hr of maternal experience also significantly disrupted maternal memory, whereas infusions in the medial preoptic area had no effect. It was concluded that the NA shell, but not the NA core, is involved in the consolidation of maternal memory. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Differential roles of dorsal hippocampal subregions in spatial working memory with short versus intermediate delay.

In order to determine the role of subregions of the hippocampus in spatial working memory, this study combined selective neurotoxic lesions of the hippocampal subregions with a simple delayed nonmatching-to-place task on a radial maze in rats. Lesions of the dentate gyrus or the CA3, but not the CA1, subregion of the hippocampus induced a deficit in the acquisition of the task with short-term delays (i.e., 10 sec) and impaired performance of the task in a novel environment. All subregional lesions produced sustained impairment in performing the task with intermediate-term delays (i.e., 5 min) when rats were tested in a familiar environment. The results suggest a dynamic interaction among the dorsal hippocampal subregions in processing spatial working memory, with the time window (i.e., delay) of a task recognized as an essential controlling factor. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Hippocampal seizures disrupt working memory performance but not reference memory acquisition.

The effect of hippocampal seizures in rats was assessed in two spatial memory tasks: The reference memory task was a simultaneous two-choice discrimination in a T-maze. The working memory task was a delayed conditional discrimination in a radial arm maze. In each task the hippocampus of each rat was stimulated to seizure after the presentation of the information to be remembered. In the reference memory task, hippocampal seizures did not impair acquisition, whether the stimulation was given immediately after or 4 hr after the presentation of the stimuli to be remembered. In the working memory task, hippocampal seizures did impair performance in a group of the same rats. These results support the distinction between a trial-dependent working memory system that requires hippocampal function and a trial-independent memory system that does not depend on hippocampal function. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Analysis of the content of configural representations: The role of associatively evoked and trace memories.

Two experiments examined the content of configural learning in rats. In Experiment 1, after simple pre-exposure to two hybrid contexts (AB and CD), rats acquired a configural discrimination involving two of the contexts (A and C) and two auditory stimuli (X and Y; AX→food, AY→no food, CX→no food, and CY→food). When rats were then placed in context B, they were more likely to respond to X than Y, and when they were placed in context D the reverse was the case. Experiment 2 demonstrated that rats can acquire a configural discrimination involving the presence of context (A) and its memory trace (a; AX→food, AY→no food, aX→no food, and aY→food). These results show that associatively provoked memories (Experiment 1) and memory traces (Experiment 2) can participate in configural discriminations. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Reciprocal interactions between intralaminar and lateral thalamic nuclei in rats

The effect of the nootropic drug piracetam (100 mg/kg) on kindled seizures, kindling-induced learning deficits, and histological alterations due to changes in central excitability was investigated in Wistar rats. The animals were kindled by repeated i.p. injections of an initially subconvulsive dose of pentylenetetrazol (PTZ). As a control, piracetam or physiological saline was given 60 minutes before PTZ. Twenty-four hours after completion of kindling the rats were tested in a shuttle-box paradigm. Seven days after the final kindling injection, the animals received a challenge dose of PTZ. Finally, the brains of the rats were processed for histological investigation. Pentylenetetrazol-kindled animals showed increasing seizure scores, and a learning deficit in the shuttle-box. Piracetam had no effect either on kindling development or on the reaction to a challenge dose of PTZ, but it protected the animals against the kindling-induced reduction of learning performance. The substance had no effect on learning performance in control animals. In distinct hippocampal structures, a neuronal cell loss was found in kindled rats. Interestingly, piracetam counteracted this damage efficaciously. The effects of piracetam are discussed in terms of its cytoprotective action. It is suggested that a coadministration of piracetam with clinically used antiepileptic drugs might be useful in antiepileptic therapy.     

Postnatal epigenetic influences on seizure susceptibility in seizure-prone versus seizure-resistant rat strains.

The creation of seizure-prone (Fast) and seizure-resistant (Slow) rat strains via selective breeding implies genetic control of relative seizure vulnerability, yet ample data also advocates an environmental contribution. To investigate potential environmental underpinnings to the differential seizure sensitivities in these strains, the authors compared amygdala kindling profiles in adult male Fast and Slow rats raised by (a) their own mother, (b) a foster mother from the same strain, or (c) a foster mother from the opposing strain. Ultimately, strain-specific kindling profiles were not normalized by cross-fostering. Instead, both strains became more seizure-prone regardless of maternal affiliation (i.e., cross-fostered groups from both strains kindled faster than uncrossed controls). Interhemispheric seizure spread was also facilitated in cross-fostered Slow rat groups and was associated with increased commissural cross-sectional areas, giving them a Fast-like profile. It is important to note, however, that all Fast groups remained significantly more seizure-prone than Slow groups, suggesting that although the postnatal environment strongly influenced seizure disposition in both strains, it did not wholly account for their relative dispositions. Investigation into mechanisms fundamental to cross–fostering-induced seizure facilitation should help prevent postnatal worsening of pathology in already seizure-prone individuals. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Cognitive deficits in docosahexaenoic acid-deficient rats.

This study investigated the influence of brain docosahexaenoic acid (DHA) deficiency on simple and complex olfactory-based learning and memory in 2nd generation (F2) adult male rats. Rats raised and maintained on either an n-3-adequate or an n-3-deficient diet were tested for acquisition of an olfactory learning set and an olfactory memory task, and for motivation to obtain a water reward. Despite a 76% decrease in brain DHA, n-3-deficient rats were able to acquire most simple 2-odor discrimination tasks but were deficient in the acquisition of a 20-problem olfactory learning set. This deficit could not be attributed to changes in sensory capacity but, instead, appeared to represent a deficit in higher order learning. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Encoding specific associative memory: Evidence from behavioral and neural manipulations.

Within-subjects procedures with rats assessed the associative structures acquired during conditioning trials in which the interval between the stimuli and food was either short or long (i.e., A–10 s→food and B–40 s→food). In Experiments 1 and 2, after these conditioning trials, A and B served as second-order reinforcers for 2 further stimuli (i.e., X→A and Y→B); whereas Experiment 3 used a sensory preconditioning procedure in which X→A and Y→B trials occurred before the conditioning trials, and rats were finally tested with X and Y. In each experiment, Y elicited greater responding at test than did X. This finding supports the contention that the long-lived trace of B (associated with food on B–40 s→food trials) is more similar to the memory of B that was associatively provoked by Y, than is the short-lived trace of A (associated with food on A–10 s→food trials) to the memory of A that was associatively provoked by X. These conclusions were reinforced by the effects of a neural manipulation that disrupted discrimination learning involving the short traces of stimuli but not the long traces of the same stimuli. (PsycINFO Database Record (c) 2011 APA, all rights reserved)     

Contributions of the retrosplenial and posterior parietal cortices to cue-specific and contextual fear conditioning.

The retrosplenial cortex (RSP) and the posterior parietal cortex (PPC) are the primary sources of cortical sensory input to the postrhinal cortex (POR) in rodents. Together, these areas compose a major corticohippocampal circuit that is involved in processing visuospatial information. The POR has been implicated in contextual learning and memory, consistent with the type of information presumably being processed by this region. By comparison, little is known about the role of the RSP or the PPC in contextual learning. In the present study, rats were trained either before or after surgery in a standard signaled fear conditioning task in which an auditory cue was paired with foot shock. Contextual fear and tone-specific fear were assessed in subsequent test sessions. In Experiment 1, electrolytic damage to the RSP either before or immediately after training impaired the expression of contextual fear but not tone-specific fear. In contrast, electrolytic damage to the PPC had no effect on conditional fear to the context or the tone in Experiment 2. These findings indicate that the RSP, but not the PPC, contributes to the processing of contextual information by the POR corticohippocampal processing stream. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Short-term rebound anxiolytic effects and long-term changes in platelet benzodiazepine binding after pentylenetetrazole-kindling in two strains of rat

Although there were no differences in response to an acute injection of pentylenetetrazole (PTZ), there were strain differences in the development of kindled seizures to repeated injections (PTZ; 30 mg/kg 3 times weekly for 13 injections), with Wistar rats reaching stage 4 or 5 of clonic-tonic seizures, but hooded Lister rats reaching only stage 2 or 3 of convulsive waves axially through the body. The strains also reacted differently to a test dose of PTZ (20 mg/kg) one week after the end of kindling, with the Wistar strain showing stage 3 and the Lister strain stage 2 seizures. When the rats were tested 24 h after the end of the kindling injections there was an anxiolytic effect in the social interaction test, in both the low light, familiar and the low light, unfamiliar test conditions that reached significance in the Wistar strain. The Wistar kindled rats showed an anxiolytic effect in the elevated plus-maze test of anxiety when they were tested 24 h after the end of kindling. The anxiolytic effects found 24 h after kindling could not be due to the seizure 24 h earlier, since no changes were found in rats tested 24 h after a single seizure from PTZ (60 mg/kg). When the rats were tested 1 week after the end of kindling there were no changes, compared with vehicle-injected controls, in either test of anxiety. There was no change in benzodiazepine binding in platelets of the kindled Lister rats but there was a significant increase in the kindled Wistar rats 1 week after the end of kindling and also 24 h after a single PTZ seizure. The pattern of increased platelet benzodiazepine binding did not correspond with the time course of rebound anxiolytic effects. However, after kindling it seems that there are long-lasting changes in benzodiazepine binding that are similar to the short-term increases that are found following a single seizure.     

Ovarian Hormones and Cognition in the Aged Female Rat: II. Progesterone Supplementation Reverses the Cognitive Enhancing Effects of Ovariectomy.

The authors hypothesized that the progesterone component of some hormone replacement therapies in women is detrimental to cognition. A previous study showed that ovariectomy (ovx) in aged rats enhanced spatial working memory and decreased elevated progesterone levels (H. A. Bimonte-Nelson, R. S. Singleton, C. L. Hunter, et al., 2003). The current study evaluated whether progesterone administration counteracts these cognitive enhancing effects of ovx. Aged sham and aged ovx rats given progesterone exhibited compromised learning of the working and reference memory components of the task, and made more working memory errors on the latter testing days compared with aged ovx rats not given progesterone. Results suggest that whereas ovx of the aged female rat enhances learning and the ability to handle numerous items of spatial working memory information, progesterone is detrimental to these aspects of performance. These findings may speak to studies in menopausal women which suggest that combination hormone therapies have a negative impact on cognition. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Adolescent cocaine residually impairs working memory and enhances fear memory in rats.

The residual effects of cocaine during adolescence on memory in male young adult rats were studied. Animals were injected with 20 mg/kg cocaine on postnatal Days 28 through 35, whereas lab-chow (LC) and pair-fed (PF) control subjects received saline. Assessment of spatial working and long-term memory in the Morris water maze, and 72-h retention of an inhibitory avoidance task was conducted at about 5 and 9 weeks postcocaine, respectively. Relative to PF control subjects, cocaine-treated subjects showed impairments in the water maze when required to swim to the hidden platform placed in a quadrant diagonal from the location of its original location (i.e., on reversal learning). These same drug-treated animals, however, exhibited enhanced inhibitory avoidance retention relative to both control groups. These seemingly disparate findings are seen as being consistent with previous data showing that cocaine during adolescence residually impairs spatial memory and leads to enhanced fear responses. Moreover, when taken with previous findings from our laboratory, the present water maze data indicate that the deleterious effects of cocaine, when administered during adolescence, is delayed until 5 weeks after initiation of abstinence. It is speculated that alterations to limbic circuitry, especially those associated with the amygdala, account for the behavioral results observed. (PsycINFO Database Record (c) 2010 APA, all rights reserved)