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Biomedical subjects

J N Rawlins

Publications and source records attributed to J N Rawlins.

At least 19 recordsLinked to original sources
PubMed1999

Dissociating pain from its anticipation in the human brain.

The experience of pain is subjectively different from the fear and anxiety caused by threats of pain. Functional magnetic resonance imaging in healthy humans was applied to dissociate neural activation patterns associated with acute pain and its anticipation. Expectation of pain activated sites within the medial frontal lobe, insular cortex, and cerebellum distinct from, but close to, locations mediating pain experience itself. Anticipation of pain can in its own right cause mood changes and behavioral adaptations that exacerbate the suffering experienced by chronic pain patients. Selective manipulations of activity at these sites may offer therapeutic possibilities for treating chronic pain.

Adult↗
PubMed1999

The effects of NMDA-induced retrohippocampal lesions on performance of four spatial memory tasks known to be sensitive to hippocampal damage in the rat.

Four separate cohorts of rats were employed to examine the effects of cytotoxic retrohippocampal lesions in four spatial memory tasks which are known to be sensitive to direct hippocampal damage and/or fornix-fimbria lesions in the rat. Selective retrohippocampal lesions were made by means of multiple intracerebral infusions of NMDA centred on the entorhinal cortex bilaterally. Cell damage typically extended from the lateral entorhinal area to the distal ventral subiculum. Experiment 1 demonstrated that retrohippocampal lesions spared the acquisition of a reference memory task in the Morris water maze, in which the animals learned to escape from the water by swimming to a submerged platform in a fixed location. In the subsequent transfer test, when the escape platform was removed, rats with retrohippocampal lesions tended to spend less time searching in the appropriate quadrant compared to controls. Experiment 2 demonstrated that the lesions also spared the acquisition of a working memory version of the water maze task in which the location of the escape platform was varied between days. In experiment 3, both reference and working memory were assessed using an eight-arm radial maze in which the same four arms were constantly baited between trials. In the initial acquisition, reference memory but not working memory was affected by the lesions. During subsequent reversal learning in which previously baited arms were now no longer baited and vice versa, lesioned animals made significantly more reference memory errors as well as working memory errors. In experiment 4, spatial working memory was assessed in a delayed matching-to-position task conducted in a two-lever operant chamber. There was no evidence for any impairment in rats with retrohippocampal lesions in this task. The present study demonstrated that unlike direct hippocampal damage, retrohippocampal cell loss did not lead to a general impairment in spatial learning, implying that the integrity of the retrohippocampus and/or its interconnection with the hippocampal formation is not critical for normal hippocampal-dependent spatial learning and memory. This outcome is surprising for a number of current hippocampal theories, and suggests that other cortical as well as subcortical inputs to the hippocampus might be of more importance, and further raises the question regarding the functional significance of the retrohippocampal region.

Animals↗
PubMed1998

A computer controlled analysis of freezing behaviour.

The conditioned freezing response in rats has been much used both by psychologists and neuroscientists to investigate the behavioural effects of brain lesions and of changes in motivational state. The primary advantage of the freezing response is that it can be used without motivational manipulations such as food or water deprivation. Previously, freezing has been measured by a human observer either from video recordings or during the test sessions themselves. But these methods of data collection have potential disadvantages. In the present paper, we describe a new, computer controlled, automated procedure for assessing conditioned freezing. Each conditioning chamber contains a mini-video camera. Behaviour is analysed on-line by means of a programme which compares every two adjacent seconds of video tape to generate a screen representing the percentage difference between them. A difference of <0.05% (50 pixels) is classified as a freezing response. Experiments are described in which we measure conditioned freezing and its development over time, in response to contextual cues and to a discrete tone which had been paired with foot shock. We demonstrate our apparatus and methods of data analysis to be sensitive to: number of tone-shock pairings, rat strain and tone pre-exposure.

Animals↗
PubMed1998

A comparison of the density of NADPH-diaphorase-reactive neurons in the fascia dentata and Ammon's horn between 6-month and 12-month old dark agouti rats.

The present study aimed to assess the developmental progress of the hippocampal nitric oxide (NO) system within adulthood by comparing the density of NO-producing neurons in the fascia dentata and Ammon's horn in two groups of adult male rats using NADPH-diaphorase (NADPH-d) histochemistry. One group comprised 6-month-old rats (early adulthood), and the other 12-month-old rats (middle-adulthood). Areal density (number of neurons per unit area) of NADPH-d positive neurons along the three hippocampal axes (septo-temporal, transverse and radial axes) were subjected to quantitative analyses. There were significant variations in the density of NADPH-d-reactive neurons along the transverse and radial axes of the hippocampus, similar to what have been described previously. Comparison between 6-month and 12-month-old rats indicated a substantial reduction in the density of NADPH-d-reactive neurons in the fascia dentata (69%) and Ammon's horn (54%) of the latter group. This reduction was relatively uniform along the septotemporal and radial axes, but appeared to be more pronounced in the fascia dentata and in the proximal region of Ammon's horn. Our finding showed that the hippocampal NO system can undergo significant changes within adulthood. It further highlighted the possibility that an age-related reduction in the capacity to produce NO may not be directly responsible for the cognitive decline associated with senescence, but rather predisposes neuronal degeneration in later life.

Animals↗
PubMed1998

The effects of cytotoxic entorhinal lesions and electrolytic medial septal lesions on the acquisition and retention of a spatial working memory task.

Rats with lesions either of medial septal nucleus (MSN) or the entorhinal cortex (ECx) were compared postoperatively with unoperated controls in a discrete-trial, delayed matching-to-position (DMTP) task, conducted on an elevated T-maze. A DMTP trial consisted of two consecutive visits to the maze: an information run and a choice run. The animals were first forced to visit a randomly selected choice arm in the information run. In the choice run, the correct response was to match the choice arm that had been visited on the information run, regardless of whether the information run itself had been rewarded or not. MSN animals failed to succeed in this task, performing at close to chance level throughout training. On the other hand, ECx rats consistently perform at a level comparable with that of unoperated controls; both groups attained more than 90% correct after 192 trials. Long-term retention testing was carried out after an intermission of 4 weeks, when the same task was re-administered to the ECx and unoperated control animals. ECx animals showed significantly less saving than controls in the retention test. In contrast, when the retention interval within a DMTP trial was increased by the imposition of a 20-s delay between the information and choice runs, the ECx group was not selectively affected by this manipulation.

Acetylcholinesterase↗
PubMed1998

The effects of hippocampal aspiration lesions on conditioning to the CS and to a background stimulus in trace conditioned suppression.

Rats with hippocampal aspiration lesions or cortical control lesions were compared to sham operated controls in a trace conditioned suppression task, in which a long-lasting background stimulus played the role of more conventional contextual cues. In all three surgical treatment groups, conditioning to the explicit conditioned stimulus (CS) decreased, but conditioning to the background cue increased, when a longer trace interval was used. There was thus no evidence of a differential partitioning of associative conditioning as a result of the lesion, despite the evident sensitivity of the behavioural paradigm to variations in the CS-->unconditioned stimulus (US) interval. This result contrasts with earlier reports using conventional contextual cues in analogous experimental designs, and so suggests that the sensitivity of contextual conditioning to hippocampal dysfunction depends at least in part on the physical nature of conventional contextual cues, and not solely on the less precise predictive information that such cues typically provide.

Animals↗
PubMed1998

A comparison between the effects of medial septal lesions and entorhinal cortex lesions on performance of nonspatial working memory tasks and reversal learning.

Rats with either electrolytic medial septal lesions or cytotoxic entorhinal lesions were compared to unoperated controls on a series of delayed matching-to-sample (DMS) tasks. A DMS trial consisted of two runs. In the first (information) run, the subject was familiarized with a sample discriminandum. In the second (choice) run, the subject was required to discriminate the sample discriminandum from a novel one. When a set of 20 discrete complex objects were used as discriminanda and each discriminandum was used once per day, neither lesions impaired choice accuracy. However, when a single pair of simple discriminanda was employed and re-used between trials within a day, rats with medial septal lesions were severely impaired whereas rats with entorhinal lesions performed at a level comparable to unoperated controls. Next, proactive interference was demonstrated by the introduction of an extra run prior to the information run. When this extra (pre-information) run required the subjects to visit the (eventual) negative discriminandum such that correct choice had to be guided by relative familiarity judgement, choice performance was reduced. Neither lesion group was selectively affected by this manipulation. But when the relative reinforcement history of the pre-information run and the information run was manipulated, such that a correct response required the subject to approach a discriminandum that had recently been non-rewarded, rats with entorhinal lesions were selectively impaired. The effect of delay was demonstrated when a 20-s interval was imposed between information run and choice run. This reduced overall choice accuracy, and this effect appeared to be more pronounced in both lesion groups, although not significantly so. Finally, neither lesion affected the acquisition of a simple discrimination task, but reversal learning was selectively enhanced in the entorhinal lesion group.

Acetylcholinesterase↗
PubMed1998

Reduced latent inhibition in people with schizophrenia: an effect of psychosis or of its treatment.

BACKGROUND: People with schizophrenia show impaired attention. This could result from reduced latent inhibition (a measure of ability to filter out irrelevant stimuli). Previous studies have found reduced auditory latent inhibition in people with acute schizophrenia: we tested whether this results from psychosis or from drug treatment. METHOD: We measured auditory latent inhibition in two studies. One compared antipsychotic-naive people with acute schizophrenia with patients within two weeks of starting antipsychotic treatment. The second compared healthy volunteers given either saline or 1.0 mg haloperidol, intravenously. RESULTS: Latent inhibition was absent in treated patients, but was clearly present in patients who were naive to antipsychotics. Latent inhibition was absent in volunteers given haloperidol, but was clearly present in those given saline. CONCLUSIONS: The reduced auditory latent inhibition seen in acute schizophrenia is more plausibly due to antipsychotic treatment than to the disorder. Unless neuropsychological models of schizophrenia incorporate evidence from drug-free patients and drug-treated healthy controls, they may be invalid.

Adult↗
PubMed1997

Neonatal nonhandling and in utero prenatal stress reduce the density of NADPH-diaphorase-reactive neurons in the fascia dentata and Ammon's horn of rats.

The density of nitric oxide (NO)-producing neurons in the fascia dentata and Ammon's horn was assessed in 6-month-old male rats using NADPH-diaphorase (NADPH-d) histochemistry. Two separate experiments investigated whether (1) the complete absence of neonatal handling or (2) the administration of periodic prenatal stress could affect the expression and distribution of NADPH-d reactivity in the hippocampus, when compared with rats raised in normal standard laboratory conditions. Experiment 1 demonstrated that adult rats that received no handling during neonatal development (from birth to postnatal day 22) showed a very substantial reduction in NADPH-d-positive neurons per unit area throughout the entire hippocampus when compared with rats that received regular daily handling in this period. Quantitative analysis further revealed that this effect was significantly more pronounced in Ammon's horn than in the fascia dentata, and within Ammon's horn the dorsal region was selectively more affected. Experiment 2 showed that prenatal stress, which involved the administration of daily restraint stress to pregnant dams throughout the gestation period, also led to a reduction in NADPH-d reactivity in the hippocampus of the offspring of these dam when they reached adulthood. The present results suggest that behavioral manipulations in the early neonatal or prenatal period can significantly alter the neurodevelopment of the hippocampal NO system and these changes might be related to some of the behavioral abnormalities that emerge later in adulthood.

Animals↗
PubMed1997

Cytotoxic lesions of the retrohippocampal region attenuate latent inhibition but spare the partial reinforcement extinction effect.

Experiment I assessed the effect of cytotoxic retrohippocampal (entorhinal and extra-subicular cortices) lesions on the development of latent inhibition (LI) using an off-the-baseline, between-subjects, conditioned emotional response paradigm. Sham-operated controls and unoperated rats that had been pre-exposed to a light stimulus prior to light-shock pairings showed less conditioned suppression towards the light stimulus than the nonpre-exposed animals, thus demonstrating LI. However, LI was not evident in rats with retrohippocampal lesions. In experiment 2, the same animals were trained to run in an straight runway for food. Half of the animals were trained under a 50% partial reinforcement schedule (i.e. they were rewarded randomly on half of the acquisition trials) and the other half were trained under a continuous reinforcement schedule (i.e. they were rewarded on every acquisition trial). When tested in extinction, animals trained on the partial reinforcement schedule showed greater persistence than animals trained on continuous reinforcement, thus demonstrating the partial reinforcement extinction effect (PREE). Rats with retrohippocampal lesions showed a PREE that was at least as clear as that seen in the sham-operated controls and in the unoperated animals. It is concluded that cytotoxic lesions of the retrohippocampal region selectively led to an abolition of LI, but spared the PREE. The present study thus provided evidence against the hypothesis that LI and the PREE share a common neural substrate.

Analysis of Variance↗
PubMed1997

Haloperidol enhances latent inhibition in visual tasks in healthy people.

We have previously shown that 0.5 mg haloperidol (i.v.) increased latent inhibition in one of two visual tasks. The present study analysed the effects of a higher dose of haloperidol (1.0 mg, i.v.) on latent inhibition in these two visual tasks in healthy volunteers in a randomised controlled trial. In the task where 0.5 mg haloperidol had enhanced latent inhibition, 1.0 mg had the same effect, thus replicating the previous result. In the task where 0.5 mg haloperidol had been ineffective, 1.0 mg haloperidol enhanced latent inhibition in high schizotypal subjects only. This indicates that subjects with higher schizotypy scores are more sensitive to dopamine blockade. A comparison of the results from the studies at the two different doses suggests a dose dependence of haloperidol's effects on latent inhibition that parallels results from animal work.

Adult↗
PubMed1997

Effects of scopolamine and hippocampal lesions on negative patterning discrimination performance in rats.

Rats were trained in operant chambers to perform an appetitive negative patterning successive discrimination. They were required to respond to the left in response to a tone or click and right to a tone-click compound. Scopolamine and methyl scopolamine impaired performance accuracy and increased response latency and response omissions. Subsequent hippocampal aspiration lesions initially impaired accuracy, which later improved. Lesions decreased response latencies. Finally, the effects of scopolamine and methyl scopolamine were shown to be similar in lesioned and control rats, suggesting that the hippocampus is not involved in the actions of these drugs on this task.

Animals↗
PubMed1997

The hippocampus, objects, and their contexts.

Rats with hippocampal aspiration lesions and controls were trained on delayed nonmatching to sample with small complex goal boxes, presented trial uniquely. A series of experiments then used pairs of large or small boxes, presented repeatedly. The lesions impaired choice accuracy when the rats were tested with large empty boxes but not when small boxes containing 3-dimensional objects were used. There was a comparable impairment when the rats were tested with pairs of large complex boxes, which contained arrays of objects, identical to those used in the smaller boxes but necessarily spaced further apart. Subsequent experiments revealed that the lesion deficit with large boxes was reduced by insertion of a continuous line of distinctive objects and eliminated by trial-unique presentation of large boxes. The results are discussed in terms of (non) spatial accounts of hippocampal function and the compensatory effects of novel object cues. We conclude that, for hippocampal rats, spatial cues, although useless, can nonetheless be profoundly disruptive.

Animals↗
PubMed1997

Intravenous administration of haloperidol to healthy volunteers: lack of subjective effects but clear objective effects.

Healthy volunteers who received i.v. injections of either saline or haloperidol (0.5 or 1.0 mg) made visual analogue scale ratings of subjective mood, tension, shakiness and the global feeling of having received an active drug. The subjective ratings of volunteers who received haloperidol did not differ, overall, from those who received saline. In contrast, the drug caused clear objective changes in several psychological tests. I.v. administration of low doses of haloperidol may permit double-blind testing of the psychological actions of haloperidol in healthy volunteers.

Affect↗
PubMed1996

Antipsychotic drug effects in a model of schizophrenic attentional disorder: a randomized controlled trial of the effects of haloperidol on latent inhibition in healthy people.

We studied the effects of haloperidol (0.5 mg, intravenously) on latent inhibition in an auditory paradigm and two visual paradigms in healthy subjects. Haloperidol increased latent inhibition in one visual paradigm and tended to increase latent inhibition in an auditory task, compared to saline-injected controls. These results indicate that haloperidol can enhance the selectivity of attention. In contrast, previous studies have reported that acute schizophrenics show reduced latent inhibition.

Acoustic Stimulation↗
PubMed1996

NADPH-diaphorase reactive pyramidal neurons in Ammon's horn and the subiculum of the rat hippocampal formation.

NADPH-diaphorase histochemistry has been shown to stain cells which contain nitric oxide synthase, an enzyme responsible for the biosynthesis of the freely diffusable gas nitric oxide. A number of studies have mapped the distribution of NADPH-diaphorase-reactive neurons in the hippocampal formation but they have failed to yield consistent data. The major point of controversy concerns the presence of NADPH-diaphorase-reactive pyramidal cells in the CA1 subfield of the rat hippocampal formation. The present results show that CA1 pyramidal neurons do contain nitric oxide synthase (NOS) which can be reliably demonstrated with the appropriate histochemical procedure. One of the critical determinants of CA1 pyramidal cell NADPH-diaphorase activity is shown to be incubation of brains in sucrose solution prior to histochemical processing. Subicular pyramidal cells were also found to contain NOS and to possess NADPH-diaphorase activity. These results explain a number of contradictory reports in the literature relating to the presence of NADPH-diaphorase activity in hippocampal principal cells. Additionally, densitometric analysis carried out on 20 microns thick sections, from brains incubated in sucrose solution, indicated that there were characteristic gradients. The intensity of NADPH-diaphorase activity in pyramidal cells located in the ventral subiculum was found to be greater than those in the dorsal subiculum. A similar, yet marginal, trend was apparent for pyramidal cells in CA1 and CA3, as well as nonpyramidal cells in CA1. At both dorsal and ventral levels, NADPH-diaphorase-positive subicular pyramidal cells and CA1 nonpyramidal cells also show a greater intensity than CA1 or CA3 reactive pyramidal neurons. This study also showed that tissue incubation in sucrose solution prior to immunocytochemistry, enhanced immunoreactivity of the endothelial isoform of NOS whilst having little effect on neuronal NOS reactivity.

Animals↗
PubMed1996

Equithesin without chloral hydrate as an anaesthetic for rats.

In 1977 it was reported that chloral hydrate could cause adynamic ileus in rats, leading to morbidity and death. The symptoms were a swollen abdomen, lethargy and anorexia. However, chloral hydrate is still used as an anaesthetic, particularly in Equithesin mixture. We report that Equithesin without chloral hydrate is an effective anaesthetic, with a slightly reduced potency compared to Equithesin itself, and anaesthesia may be maintained for several hours by supplemental doses.

Anesthesia↗