Dose-related ethanol-like effects of the NMDA antagonist, ketamine, in recently detoxified alcoholics

AIMS: To study the clinical and histopathological features of sclerosing epithelioid fibrosarcoma, and to define diagnostic criteria for this uncommon soft-tissue tumour. METHODS AND RESULTS: Standard histological, immunohistochemical and ultrastructural techniques were applied to five tumours from head and neck, chest wall and groin. Tumours consisted of groups of monomorphic rounded/epithelioid cells surrounded by a prominent collagenous stroma. Tumour cells showed positive vimentin staining but were negative for other markers. They contained prominent rough endoplasmic reticulum and a large Golgi apparatus which in one case was producing collagen secretion granules, an ultrastructural marker for collagen production. Three patients had medium to long-term survival (3-7 years). Of these, one was disease-free for 3 years, and two experienced multiple recurrences: one of the latter died of metastatic disease. CONCLUSION: Criteria for diagnosing this uncommon tumour include: small to medium cell size, clear or pale cytoplasm, cellular arrangement in cords and strands, dense collagenous stroma; vimentin staining; rough endoplasmic reticulum and a Golgi apparatus producing, in well preserved examples, collagen secretion granules. The paper emphasizes the value of electron microscopy, supporting an appropriate histological picture and immunophenotype, in identifying these relatively low-grade sarcomas.     

Culture and the cognitive and neuroendocrine responses to speech.

The present research investigated cultural differences in the psychological and biological effects of verbalization of thoughts. Three studies tested how verbalization of thoughts requires a different amount of effort for people from cultures with different assumptions about speech and examined implications for the cognitive performance and stress hormone response to the task. The results showed that verbalization impaired East Asians/East Asian Americans' performance when the task was difficult but not when the task was easy, whereas the effect of verbalization on European Americans' performance was neutral or positive regardless of task difficulty. Moreover, verbalization decreased the level of cortisol response to the task among European Americans but not among East Asian Americans. The results demonstrate how the same act that is intended to create the same psychological experience could inadvertently lead to systematically different psychological experiences for people from different cultures. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Parallel perceptual/cognitive functions in humans and rats: Space and time.

Examined 24 dark- (DR) and 24 light-reared (LR) male rats' ability to learn discriminations involving location of sounds or lights. Auditory signals were more effective and more salient in terms of establishing stimulus-response associations. Visually inexperienced DR Ss learned initial discriminations as rapidly as their LR controls except under ipsilateral response conditions with light signals. Visually naive DR Ss failed to demonstrate as much cross-modal transfer as did visually experienced LR Ss. (French abstract) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Multiple limbic regions mediate the disruption of prepulse inhibition produced in rats by the noncompetitive NMDA antagonist dizocilpine

Prepulse inhibition (PPI), a phenomenon in which a weak prestimulus decreases the startle response to an intense stimulus, provides an operational measure of sensorimotor gating (a process by which an organism filters sensory information) and is diminished in schizophrenia and schizotypal patients. The psychotomimetic phencyclidine and its potent congener dizocilpine are noncompetitive antagonists of the NMDA receptor complex, and they disrupt PPI in rodents, mimicking the clinically observed PPI deficit. The neuroanatomical substrates mediating the PPI-disruptive effects of noncompetitive NMDA antagonists are unknown. The present study sought to identify brain regions subserving the disruption of PPI produced by noncompetitive NMDA antagonists in rats. PPI was measured in startle chambers immediately after bilateral infusion of dizocilpine (0, 0.25, 1.25, and 6.25 microgram/0.5 microliter/side) into one of six brain regions: amygdala, dorsal hippocampus, medial prefrontal cortex, nucleus accumbens, ventral hippocampus, and dorsomedial thalamus. Dizocilpine significantly decreased PPI after infusion into the amygdala or dorsal hippocampus. A trend toward PPI disruption was observed with administration into medial prefrontal cortex. In contrast, no change in PPI was produced by dizocilpine infusion into nucleus accumbens, ventral hippocampus, or dorsomedial thalamus. Startle reactivity was increased by dizocilpine infusion into amygdala, dorsal hippocampus, nucleus accumbens, and dorsomedial thalamus, but not medial prefrontal cortex. These findings indicate that multiple limbic forebrain regions mediate the ability of noncompetitive NMDA antagonists to disrupt PPI and that the PPI-disruptive and the startle-increasing effects of dizocilpine are mediated by different central sites.     

NMDA antagonist effects on the development of L-DOPA behavioal sensitization in rats.

This study, which used an animal model of Parkinsonism, evaluated whether the N-methyl-D-aspartate (NMDA) antagonist MK-801 can prevent the development of L-3-4-dihydroxyphenylalanine ({l}-DOPA) sensitization. In separate groups, rats with unilateral 6-hydroxydopamine (6-OHDA) lesions were treated with saline, 25 mg/kg {l}-DOPA methyl ester, 0.1 mg/kg MK-801, or MK-801 plus {l}-DOPA once per day for 13 days beginning 18–20 hrs postoperatively, well before the onset of denervation supersensitivity. Following 14 days of withdrawal, all treatment groups were given a saline test and on the next day, an {l}-DOPA challenge test. Contralateral rotation, the behavioral index of denervation supersensitivity, emerged on Day 7 in both {l}-DOPA groups. However, on the {l}-DOPA challenge test, only the {l}-DOPA group showed enhanced contralateral rotations compared with a drug-naive group. In contrast, the MK-801 and MK-801/{l}-DOPA groups were indistinguishable from the drug-naive {l}-DOPA-treated rats. These findings indicate that although MK-801 treatment did not prevent the development of behavioral sensitization to the {l}-DOPA treatment, it did prevent its persistence following drug withdrawal. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Interactive effects of subanesthetic ketamine and subhypnotic lorazepam in humans

Ketamine is an N-methyl-D-aspartate (NMDA) receptor antagonist with psychotogenic and dissociative effects in healthy humans. These cognitive and perceptual effects in humans are reportedly reduced by benzodiazepine premedication. This study assessed the interactive effects of a ketamine (i.v. bolus of 0.26 mg/kg followed by an infusion of 0.65 mg/kg per hour) and lorazepam 2 mg., PO, in humans. Twenty-three healthy subjects completed 4 test days involving the oral administration of lorazepam or matched placebo 2 h prior to the i.v. infusion of ketamine or placebo. Ketamine: 1) produced behaviors similar to the positive and negative symptoms of schizophrenia as assessed by the Brief Psychiatric Rating Scale (BPRS); 2) evoked perceptual alterations as measured by the Clinician-Administered Dissociative States Scale (CADSS); 3) impaired performance on the Wisconsin Card Sorting Test (WCST) and other tests sensitive to frontal cortical impairment; and 4) had amnestic effects. Lorazepam produced attention impairments, concrete proverb interpretations, and recall impairments. Lorazepam reduced ketamine-associated emotional distress and there was a non-significant trend for it to decrease perceptual alterations produced by ketamine. However, it failed to reduce many cognitive and behavioral effects of ketamine, including psychosis. Further, lorazepam exacerbated the sedative, attention-impairing, and amnestic effects of ketamine. There was no evidence of pharmacokinetic interaction between these medications. These data suggest that subhypnotic lorazepam and ketamine show a spectrum of interactive effects, ranging from antagonism to potentiation.     

New perspectives on the effects of action on perceptual and cognitive development.

This special section was motivated by a resurgence in the view that it is impossible to investigate perceptual and cognitive development without considering how it is affected by, and intertwined with, infants' and children's action in the world. This view has long been foundational to the field, yet contemporary investigations of the effects of acting on cognition and perception have been limited. The research showcased in this section indicates that this trend is changing as researchers consider anew the ways in which cognition derives structure from action. The work presented here illustrates the breadth of these potential effects across ages and domains of development, and it highlights the breadth of methods that can be recruited to investigate them. This new research focus provides insight for the mechanisms by which action affects perception and cognition and at the same time reveals that much remains to be learned. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Assessment of agonist and antagonist effects of tramadol in opioid-dependent humans.

The subjective, behavioral, and physiologic effects of racemic tramadol, an analgesic with low abuse liability and dual mu-opioid agonist and monoamine reuptake actions, were evaluated in 2 clinical pharmacology studies in dependent opioid abusers. In the withdrawal precipitation study, participants (N = 8) were maintained on methadone 60 mg/day orally and challenged with intramuscular tramadol, hydromorphone, naloxone, and placebo 20 hr after methadone administration. In the withdrawal suppression study, participants (N = 6) were maintained on hydromorphone given orally 10 mg 4 times daily, and spontaneous opioid withdrawal was produced by withholding doses for 23 hr. During the experimentally induced withdrawal, oral tramadol, hydromorphone, naltrexone, and placebo were given. In both studies a comprehensive panel of participant-rated, observer-rated, and physiologic measures were collected. In both studies, naloxone and naltrexone significantly increased measures of opioid withdrawal, whereas tramadol showed no discernible antagonist effects. In contrast, tramadol's pattern of effects was more similar to that of hydromorphone and suggestive of mild opioid-agonist effects (withdrawal suppression), though not to a statistically significant degree. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Modeling the effects of the NMDA receptor antagonist MK-801 on timing in rats.

The NMDA receptor antagonist MK-801 produces different effects on timing tasks. In particular, MK-801 produces an underestimation of duration when animals are tested with the differential reinforcement of low rate of responding (DRL) schedule and an overestimation of duration when animals are tested with the peak-interval (PI) procedure. The goal of this study was to develop a model-based explanation for this discrepancy. Two computer simulations were conducted via an implementation of scalar expectancy theory (SET). In Simulation 1, SET was used to provide a quantitative account of PI timing data. Simulation 2 used parameter estimates from Simulation 1 to predict effects of MK-801 on the DRL task. DRL predictions provided a close match to previous empirical data. Results of the simulations suggest that differences in the literature are likely due to inherent differences between PI and DRL tasks, rather than fundamental differences in timing. Overall, the role of NMDA receptors in timing appears to be multifaceted, impacting perception, memory, and decision processes. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Serotonin1A receptor activation by flesinoxan in humans. Body temperature and neuroendocrine responses

The effects of the selective 5-HT1A receptor agonist flesinoxan on neuroendocrine function, temperature, and behavior were assessed in male healthy volunteers using a double-blind, placebo-controlled crossover design. Flesinoxan (7 and 14 micrograms/kg), administered intravenously in 11 healthy volunteers, elicited a dose-related decrease in body temperature and increases in growth hormone, adrenocorticotropic hormone (ACTH), cortisol, and prolactin plasma levels. In a second independent study, 12 healthy volunteers were pretreated sequentially, at one-week intervals, with either the 5-HT1A antagonist pindolol (30 mg, PO), the nonselective 5-HT1/2 antagonist methysergide (4 mg, PO), or placebo, prior to being administered flesinoxan (1 mg, IV). The growth hormone response to flesinoxan was blocked by pindolol but not by methysergide, whereas the prolactin response was blocked by methysergide but not by pindolol. The ACTH and cortisol responses to flesinoxan were potentiated by methysergide. The flesinoxan-induced hypothermia was attenuated by both methysergide and pindolol, although the latter effects did not reach statistical significance. The present results suggest that the growth hormone response and the hypothermic response to the intravenous infusion of flesinoxan may serve as a valid index of 5-HT1A receptor function in humans.     

Infant perceptual, cognitive, and motor behaviours as predictors of subsequent cognitive and language development.

In a longitudinal study, 80 preterm and 68 full-term infants were administered the Bayley Scales of Infant Development at 4, 8, 12, 18, and 24 mo; the Uzgiris-Hunt Scale at 4, 8, 12, and 18 mo; the Caldwell Inventory of Home Stimulation (HOME) at 12 mo; the Reynell Language Scales at 24, 30, and 36 mo; and the Stanford-Binet Intelligence Scale at 30 and 36 mo. There were significant correlations between the early infants tests and the Stanford-Binet and the Reynell Language Scales at 30 and 36 mo, indicating continuities in cognitive development. The perceptual items of the Bayley were significant predictors early in development; at 8 mo the conceptual items became predictive, and at 12 mo the language items became predictive. The Psychomotor Development Index of the Bayley and the Means and Object Concept subtests of Uzgiris-Hunt administered at 4 and 8 mo were significantly correlated with subsequent language development. The HOME scale was significantly correlated with cognitive and language scores, particularly language comprehension. There appear to be substantial continuities between infant behaviors and cognitive and language abilities in early childhood. (French abstract) (20 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

A review of the effects of opioids on psychomotor and cognitive functioning in humans.

The literature on the effects of opioids on psychomotor and cognitive functioning in humans is evaluated. Some studies have examined the acute and chronic effects of various opioids on different subject populations. In addition, epidemiologic studies have examined the neuropsychological functioning and the risk of accidents for persons who have (or have had) opioids in their systemic circulation. In general, it appears that some opioids (mixed agonist-antagonists) more than others (morphine or codeine) impair psychomotor and cognitive functioning in healthy volunteers who have no history of opioid abuse. However, perhaps because of tolerance mechanisms, those who use opioids occasionally or habitually (patients with chronic pain or opioid abusers) are much less likely to have impairment of psychomotor or cognitive processes by opioids. Past research and present gaps in knowledge are used to make recommendations regarding worthwhile future directions in research. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

The cerebellum and cognitive functions in humans.

Recent neuropsychological studies have given rise to the hypothesis that the cerebellum is involved in nonmotor cognitive functions. The interpretation of these findings is, however, restricted by methodological problems, such as heterogenous patient samples. The present study compared patients with pathology confined to the cerebellum and patients with combined cerebellar and brainstem lesions to matched normal controls on a range of memory and learning tasks. Two procedural learning tasks were also conducted, involving perceptual (mirror reading) and conceptual (the Tower of Hanoi task) skill acquisition. Patients with damage to both cerebellum and brainstem, but not patients with cerebellar pathology alone, showed impairments on memory and visuoconstructive tasks and evidence of frontal lobe dysfunction. Cerebellar damage had no effect on skill acquisition. These results do not support the hypothesis of cerebellar involvement in procedural learning per se. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Contribution of age, genes, and environment to the relationship between perceptual speed and cognitive ability.

The aim of this study was to examine genetic influences on cognitive ability in adulthood in the context of the relationship between perceptual speed and cognitive aging. Quantitative genetic analysis of data from the Swedish Adoption Twin Study of Aging allowed for estimation of the contribution of age, genetic, and environmental effects to the variance in a latent cognitive factor and to the covariance between the cognitive factor and perceptual speed. The sample included 292 pairs of monozygotic and dizygotic twins, both reared together and reared apart, ranging in age from 40 to 84 years. Analysis of components of total variance in the cognitive factor indicated that 90% of the age-related variance in the cognitive factor was shared with perceptual speed and 70% of the genetic variance in the cognitive factor was shared with perceptual speed. The correlation between the speed and cognitive factors was primarily genetically mediated. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Attributional, perceptual, and affective responses to depressed and nondepressed marital partners.

Husbands of wives with (n?=?22) or without (n?=?23) a history of a depressive disorder indicated their attributions about and affective reactions to real and hypothetical positive and negative events occurring to their wives, rated their wives on personality traits categorized as depression-related and depression-neutral, and reported their own marital satisfaction. Husbands of depressed, relative to nondepressed, wives made more dispositional attributions, reported more negative affect in reaction to negative events, and indicated less marital satisfaction. Depressed wives were rated more negatively on both depression-related and depression-neutral personality traits. Results are interpreted as suggesting that spouses of depressed wives have a generalized negative view of their wives, which may also be operating within distressed marriages. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

The interaction of ethanol and delta9-tetrahydrocannabinol in man: effects on perceptual, cognitive and motor functions

Twelve paid student volunteers (8 male, 4 female) were used in a double-blind crossover experiment to investigate the effects of delta9-tetrahydrocannabinol (THC) alone, and in combination with ethanol, on human perceptual, cognitive and motor functions. Both THC (10 mg/70 kg) and ethanol (0-5 g/kg) had little effect when administered alone. The combination of drugs, however, induced a significnat decrement in performance in some of the tests and this interaction was considered to be at least additive. The peak blood ethanol concentration was higher (P = 0-05) when subjects received both ethanol and THC than when they received ethanol alone.     

Responses to cognitive and perceptual ambiguity in chronic and acute schizophrenics.

Responses of 25 acute and 34 chronic schizophrenics to perceptual and cognitive ambiguity were compared with those of 36 normal control Ss by means of: several "decision location" series consisting of blurred photographs presented in the order of increasing clarity; a series of pictures which could be matched, at Ss' discretion, with a number of statements allegedly made by the persons pictured; a series of pictures to be similarly matched with nationality names. The chronic Ss compared to normals offered earlier recognition responses on the perceptual task and matched more items on the cognitive measures. The scores of the acute group, however, yielded uniformly negative results and were found to be intermediate in relation to those of the chronic and normal Ss. (31 ref.) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Effects of psychotropic medication on selected cognitive and perceptual measures.

Assessed the effects of antipsychotic drugs on schizophrenic (SZ) and affective disordered (AD) patients (mean age 28.1 yrs) who completed 11 cognitive tests, including 4 subscales of the WAIS. Two hospital experimental groups (SZs and ADs), 2 hospital comparison groups (SZs and ADs), and a normal control group (mean age 28.7 yrs) were tested on 2 occasions. The 34 experimental SZ Ss and the 26 experimental AD Ss were removed from all medication for 3 wks and were then tested; they were tested again 4 wks after being placed on their prescribed therapeutic drugs. The 13 control SZ Ss and the 6 control AD Ss were tested twice, 4 wks apart, and medicated on both occasions. The 26 normal, drug-free controls were also tested twice, 4 wks apart. Results show the following: (1) During drug-free periods, there were significant differences between drug-free and drug-treated Ss, attributable most likely to generalized deficits. (2) Medication did not affect performance on the tests in any manner. (3) Presence or absence of clinical improvement did not account for performance on these measures. (4) The test performance of Ss already on drugs changed in ways that were very similar to those of Ss who are first off drugs and then put on drugs. (47 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Neuroanatomical and cognitive mediators of age-related differences in perceptual priming and learning.

Our objectives were to assess age differences in perceptual repetition priming and perceptual skill learning and to determine whether they are mediated by cognitive resources and regional cerebral volume differences. Fragmented picture identification paradigm allows the study of both priming and learning within the same task. The authors presented this task to 169 adults (ages 18–80), assessed working memory and fluid intelligence, and measured brain volumes of regions that were deemed relevant to those cognitive skills. The data were analyzed within a hierarchical path modeling framework. In addition to finding age-related decrease in both perceptual priming and learning, the authors observed several dissociations with regards to their neural and cognitive mediators. Larger visual cortex volume was associated with greater repetition priming, but not perceptual skill learning, and neither process depended upon hippocampal volume. In contrast, the volumes of the prefrontal gray and white matter were differentially related to both processes via direct and indirect effects of cognitive resources. The results indicate that age-related differences in perceptual priming and skill learning have dissociable cognitive and neural correlates. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Effects of the NMDA receptor antagonist MK-801 on short-interval timing in rats.

Effects of MK-801, an N-methyl-D-aspartate antagonist, on short-interval timing were examined using the peak-interval (PI) and PI-gap procedures. Fisher 344 rats were given daily injections of 0.025 mg/kg, 0.05 mg/kg, and 0.2 mg/kg MK-801. The main results were (a) 0.2 mg/kg MK-801 produced an immediate overestimation of the criterion time; (b) MK-801 increased peak rate of responding; (c) 0.2 mg/kg MK-801 produced an increase in variability; (d) during the PI-gap procedure, a reset pattern was observed for all rats (MK-801 and saline). Results suggest that MK-801 has at least 2 effects. First, MK-801 interferes with short-interval timing by producing an overestimation of time and a nonscalar increase in variability. Second, MK-801 increases response rate, suggesting a decrease in response inhibition. (PsycINFO Database Record (c) 2010 APA, all rights reserved)