D-cycloserine and early ethanol exposure in developing rats.

Pregnant rats were exposed to one of the following treatments: 20% aqueous sucrose (w/v; Control), 20% aqueous sucrose with 20 mg D-cycloserine (DCS), 20% aqueous sucrose with 5% ethanol (ETH), or 20% aqueous sucrose with both 20 mg DCS and 5% ethanol (DCS+ ETH). Treatments were delivered in 20 ml of drinking water provided daily, as pilot work had determined that this was the average daily water consumption for female rats. Treatments began on Day 10 or 11 of pregnancy and terminated on postnatal Day 10. As juveniles, offspring were tested for activity in an open field and motor coordination using a rotating rod. Ethanol and DCS+ Ethanol groups were the most active groups in the open field, and DCS and DCS+ Ethanol groups had fewer falls than the Control and Ethanol groups on the rod test. Results suggest that DCS might provide protection from ethanol's adverse effects on some developmental behaviors.

Endocannabinoids and exercise.

Exercise induces changes in mental status, particularly analgesia, sedation, anxiolysis, and a sense of wellbeing. The mechanisms underlying these changes remain unknown. Recent findings show that exercise increases serum concentrations of endocannabinoids, suggesting a possible explanation for a number of these changes. This article provides an overview of this emerging field.

Visual categorical perception by rats with temporal, striate, or sham ablations.

Rats were trained to discriminate a 0 degrees stripe from a 90 degrees stripe in a two choice water maze. They were prepared with either Te2/3, partial striate (PS), or sham lesions and retrained on the preoperative discrimination. In two separate experiments, excellent savings was observed for all groups. Next, trials were administered with novel stripe orientations defined as either between- or within-category problems. Performance accuracy eroded rapidly for all groups in the first experiment, and no between-group differences were observed. In the second experiment, each session with categorical stimuli was preceded by four reminder trials with the original stimuli. This improved accuracy for all groups, but it was found that animals with PS lesions, not animals with T2/3 lesions, were impaired on between-category judgements. The impairment was not secondary to a disruption of basic visual sensory processing or significantly larger lesions relative to the Te2/3 group. As is the case for monkeys, accuracy with within-category stimuli was inferior to between-category stimuli for all groups. Possible reasons for this inter-species difference are discussed.

Further support for using the dementia rating scale in the assessment of neuro-cognitive functions of individuals with mental retardation.

The utility of the Dementia Rating Scale (DRS) when administered to individuals with mental retardation (MR) was examined. Our sample was comprised of individuals residing in an intermediate care facility in the southeastern United States, included individuals diagnosed with mild, moderate, or severe MR, and consisted of both Caucasians (50%) and individuals of African-American descent (50%). Descriptive statistics for the DRS Total Score and five subtests (e. g., Attention, Initiation/Perseveration, Construction, Conceptualization, and Memory) obtained from our sample of individuals with mild MR compared favorably with previously published values. The group with mild MR performed significantly better than the group with moderate MR on the Total Score and all subtests except Construction, and the group with moderate MR performed significantly better than individuals with severe MR on all measures. These results show that the DRS can provide information about the cognitive strengths and weaknesses of individuals with mental retardation, and they show that the DRS can be administered to a wide range of individuals diagnosed with MR.

Mental health outcomes in dually diagnosed individuals with mental retardation assessed with the MMPI-168(L): case studies.

Recently it has been shown that oral administration of the MMPI-168(L), with simplified explanations of the items provided when needed, can reveal information related to personality and psychopathology in many individuals with mental retardation. The results of repeated administrations of the inventory to 7 clients residing in an institutional setting over a period exceeding 3 years in some cases are presented here. It is argued that results obtained by repeated administration the MMPI-168(L) can reveal information concerning changes in mental health status for many individuals with mental retardation.

A strategy for screening memory functions in individuals with mental retardation.

In an attempt to develop a protocol for evaluating mentally retarded clients from a neurobehavioral perspective, a strategy for screening complex verbal, simple verbal, simple visual, and spatial working memory was developed. This strategy results in numeric values on each of the aspects of memory, and it can contribute to a "global index" of memory function. The strategy is described so that it might be adopted by other practitioners interested in screening their client's ability to store and retrieve newly acquired information. Descriptive data for 125 persons carrying diagnoses of mild, moderate, and severe mental retardation are presented. The procedure was found to discriminate well between the various levels of mental retardation, correlate reasonably well with IQ, and possess relatively good test-retest reliability.

Areas of convergence and discordance between the MMPI-168 and the Reiss Screen for Maladaptive Behavior in mentally retarded clients.

The Reiss Screen for Maladaptive Behavior and a modified version of the MMPI-168 were administered to 65 residents of a state mental institution diagnosed with mild or moderate mental retardation. Possible associations between the two screening instruments were then examined. Significant correlations were obtained between four scales of the Reiss Screen and Scales F, K, 1, 6, and 7 of the MMPI-168. These results support the clinical efficacy of both instruments in screening for behavioral pathology in mentally retarded persons. However, some scales purported to assess similar psychological constructs failed to show expected positive associations.

Ginseng improves strategic learning by normal and brain-damaged rats.

Adult rats were prepared with either sham or medial prefrontal cortex lesions and administered, beginning on the third post-operative day, either, 0, 40, or 80 mg kg-1 crude ginseng extract suspended in saline daily for the next 30 days. Later, kinetic functions were evaluated on an elevated rotating rod. No long-term influences of the treatments were observed on this task. Significant positive influences of ginseng were observed in the position reversal task. The learning deficits observed in the saline control brain-damaged rats were significantly attenuated in the ginseng-treated animals. An analysis of trial 2 response accuracy across reversals revealed enhanced cognitive abilities (i.e. acquisition of a win-stay, lose-shift strategy) in both the brain damaged and sham control rats administered ginseng. Generally, administration of the higher dose resulted in better performance in the learning paradigm. The exact mechanism responsible for these promising results remains to be discovered. Several possible mechanisms are discussed.

Construct validity of the MMPI-168(L) with mentally retarded adults and adolescents.

Fifty-three persons residing in an institution and diagnosed with mild or moderate mental retardation were assessed with a modification of the MMPI-168. Forty-one of the residents also had psychiatric diagnoses. Construct validity of the MMPI-168(L) was examined by correlating T scores obtained on the scales of this instrument with the results of an 8-item "Behavioral Survey." The survey required unit clinicians to rate the severity of behavioral disturbance in eight categories. Six of the items on the "Behavioral Survey" were found to correlate with one or more MMPI scales. Stepwise multiple regression procedures revealed additional collective relations between elevations on the MMPI and ratings of behavioral disturbance.

The flexible use of multiple cue relationships in spatial navigation: a comparison of water maze performance following hippocampal, medial septal, prefrontal cortex, or posterior parietal cortex lesions.

Rats prepared with lesions of the prefrontal cortex, posterior parietal cortex, hippocampus, or medial septal area were tested for acquisition of a number of variations of the open-field water maze using a version of place learning assessment described by Eichenbaum, Stewart, and Morris (1991). Specifically, the individual role of the aforementioned cortical and subcortical structures in tasks with differing representational demands on navigation were assessed. The results suggest that the sham-operated control, posterior parietal cortex-lesioned rats, and medial septal area-lesioned rats were able to navigate effectively under changing task conditions. Conversely, the navigational performances of the prefrontal cortex- and hippocampal formation-lesioned rats were impaired when task demands changed. The results are discussed in terms of the flexible use of multiple distal cues to guide navigation and the resulting loss of this flexibility after lesions to either the prefrontal cortex or the hippocampus.

Criterion-related diagnostic validity and test-retest reliability of the MMPI-168(L) in mentally retarded adolescents and adults.

Sixty-three persons residing in an institution and diagnosed with mild or moderate mental retardation were assessed with a modification of the MMPI-168. Fifty-one of the residents also had psychiatric disturbances. The residents were divided into three categories on the bases of pre-existing DSM III-R diagnoses. The categories were "psychotic," "executive control dysfunction," and "other-control." Significant differences were observed between the psychotic group and the other-control group on scales F, K, 6, and 8. Reevaluations were conducted four to 22 months later (MDN = 12 months). Significant test-retest reliability was found with scales L, F, K, 1, 4, 5, 6, 7, 8, and 9. The MMPI-168(L) can serve as an objective instrument in the assessment of thought disturbance and personality in mentally retarded persons.

Chronic administration of ORG 2766 for 6 months produces a subtle impairment in strategic learning by rats.

Rats were administered saline or 10 micrograms of the ACTH4-9 analog ORG 2766 on alternate days for 160 days (i.e. 80 injections total). Behavioral assessments began 1 week later. Locomotor competence was assessed by examining the number of slips and falls made by the animals on a rotating rod. The rats were also trained on a position task and 10 subsequent position reversals in a 'T' shaped water maze. Exposure to ORG 2766 failed to affect either locomotor competence or the overall number of errors committed while learning the original position habit and 10 reversals. However, the response accuracy of the ORG 2766-treated animals on trial 2 of the reversals was equivalent to that expected by chance (58% correct choices), whereas saline-treated animals effectively altered their behavior after experiencing nonreinforcement on the initial trial of a reversal (77% correct choices). This result is consistent with other observations revealing that ORG 2766 can influence attention and, therefore, some cognitive functions.

Unilateral injury of posterior parietal cortex and spatial learning in hooded rats.

The influences of bilateral or unilateral injuries within the posterior parietal cortex (PPC) upon spatial learning in a water maze were examined in three experiments. Place-learning and response-learning were investigated in a four-alley 'Greek-cross' shaped water maze with extra-maze visual cues available. No differences were detected on any of several measures sensitive to learning between the lesion groups on the place-learning task. Microanalysis of behavior within trials revealed that animals with either bilateral or right unilateral PPC injuries committed significantly more total errors, initial alley entrance ('reference memory') errors, and re-entry ('working memory') errors in the response-learning paradigm than did either the control or left PPC-injured rats. No differences were detected between the latter two groups on these measures. Unilateral lesions resulted in asymmetrical placing responses ipsilateral to the injury 10 days after surgery whereas bilateral injuries resulted in asymmetrical placing with mixed directionality. The acquisition of the response-learning problem in the absence of visual cues was studied on animals prepared with unilateral lesions and housed post-operatively either in isolation or in a 'complex environment.' In the absence of visual cues both right and left PPC-injured rats committed more errors than sham controls, and differential post-surgical housing did not attenuate these impairments. These same animals were trained on the landmark navigation task. Although no differences appeared between the lesion groups, a generalized but transient facilitation of learning was observed in animals housed in the 'complex' environment. Unilateral injuries placed in sham controls failed to disturb retention of the landmark navigation strategy. Because none of the PPC-injured animals were deficient in the landmark task, a result which is contrary to observations in other laboratories, the influence of post-surgical recovery interval upon acquisition of the landmark navigation strategy was explored. Animals were prepared with right PPC injuries and trained following either a 5 or 35 day recovery interval. Only those animals limited to the short recovery interval proved to have a spatial deficit in the landmark task. It is concluded that injuries in the PPC of either hemisphere disturb egocentric spatial functions. However, animals with left PPC injuries are able to compensate by using allocentric visual cues if they are available. It is due to the special role played by the right PPC in complex visuospatial functions that animals with this injury are unable to compensate.

A visuospatial dysfunction following posterior cortex injury is attenuated by postinjury administration of the ACTH4-9 analog ORG 2766.

Rats were trained in a Y-shaped water maze to discriminate a light gray from a medium gray visual stimulus. The latter stimulus card cued the location of a nonvisible escape platform. The animals received either a sham operation or a large ablation in the posterior neocortex, and osmotic minipumps were implanted subcutaneously in the animal's back. The pumps chronically administered either saline or ORG 2766 at a rate of 0, 1, or 10 micrograms per 24 h for 14 days while the animals recovered in individual rat cages. Four weeks after surgery retention of the discrimination was tested and, for those reattaining criterion, transposition of the habit to a pairing of the medium gray card with a black stimulus card was assessed. Animals treated with 10 micrograms ORG 2766 reattained criterion on the original discrimination more rapidly than did animals treated with 0 or 1 microgram. Neither the lesion nor the drug resulted in consistent influences upon transposition. There was no evidence that the drug protected neurons within the dorsal lateral geniculate nuclei. Postinjury treatment with some doses of ORG 2766 can attenuate the severity of some dysfunctions that accompany neurotrauma by influencing the development of behavioral compensation.

Non-spatial learning following posterior parietal or hippocampal lesions.

Posterior parietal, hippocampal, or sham-lesioned rats were tested for the acquisition of a non-monotonic serial learning task. The performance of control rats and those with a posterior parietal lesion was similar, while those with hippocampal damage demonstrated a working memory deficit. The results are integrated with contemporary conceptualizations of hippocampal and posterior parietal cortex involvement in learning and memory for non-spatial tasks.

Spatial learning following posterior parietal or hippocampal lesions.

Rats with either posterior parietal (PPC) or dorsal hippocampal (HIP) lesions were tested for open-field activity, acquisition of a multiple T water maze habit, and presence of a 'cognitive map' of the water maze arena. The performances of control and PPC-lesioned rats were similar on all behavioral measures. However, the HIP-damaged rats demonstrated higher levels of general activity, severe deficits in both working and reference memory in the multiple T water maze task, and failed to develop a cognitive map of the water maze arena.

The influences of fragments and analogs of ACTH/MSH upon recovery from nervous system injury.

Post-injury treatment with some fragments and analogs of the adrenocorticotropic hormone (ACTH) can influence recovery after nervous system injury. This review considers both the successful and unsuccessful attempts to facilitate neural and behavioral recovery from nervous system damage via post-injury administration of these compounds. To date no single unifying explanation for the mixed results observed in animals prepared with forebrain injuries has been achieved. Several possible explanations for the variety of observations reported and several potentially productive avenues for future research are suggested.

Visual memory and visual spatial functions in the rat following parietal and temporal cortex injuries.

Adult rats were prepared with either posterior parietal, temporal, or sham neocortical lesions, and after assessing gross locomotor functions, trained in cognitive visual tasks. Training was conducted in a modified circular water maze wherein the water was made opaque with a white nontoxic powder paint. The order of the tasks was counterbalanced within groups. One task was a visual matching-to-sample problem with an intertrial interval of 20 s. The second task was a visual spatial conditional problem in which visual stimuli (white or gray cards) cued spatial choices in a T maze that was inserted into the tank. After completing these tasks, the animals were trained on a simple visual pattern discrimination and a simple position habit. Both lesion groups demonstrated significant deficits on both cognitive tasks. Since gross visual perceptual, spatial, and motor abilities were found to be unaffected by the lesions, it is suggested that a generalized retardation in cognitive functions follows injuries in these sites. Also, qualitative evidence supported the conclusion that posterior parietal cortex plays an important role in integrating visuospatial stimuli with motor responses.

Visual-spatial functions persist following temporal and posterior parietal cortex lesions in rat.

Adult rats were prepared with either posterior parietal, temporal, or sham neocortical lesions. Gross kinetic functions and equilibrium were assessed on alternate days for 12 days following surgery by placing the animal on an elevated rod (3.5 cm diameter) oriented 20 degrees to horizontal and rating locomotor functions. Although all groups improved with experience and time postsurgery, rats with posterior parietal lesions exhibited a greater kinetic disturbance throughout the testing period. After a 3-week recovery period, the animals were trained on a visual-spatial task in which a visual stimulus located at the choice point cued whether the escape platform was located in the left or right arm of a T-maze. Animals were trained at a rate of 20 trials per day until a criterion of 18 correct responses in a series of 20 trials was observed. This task differed from that used in a similar previous study in this laboratory (1) in that stimulus saliency was increased and rats were punished for errors by confinement to the incorrect alley for 15 s when errors were made. All rats learned the task, and although there were subtle differences in the rate of acquisition between the groups, there were no gross differences on any of several measures of learning and performance. It is concluded that, under appropriate conditions, rats with injuries in these posterior association regions can learn and perform a task requiring the execution of different spatial responses on the basis of visual landmark cues that are spatially discontiguous from the escape site.