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R M Deacon

Publications and source records attributed to R M Deacon.

16 recordsLinked to original sources

A comparison of 129S2/SvHsd and C57BL/6JOlaHsd mice on a test battery assessing sensorimotor, affective and cognitive behaviours: implications for the study of genetically modified mice.

Mice from the 129S2/SvHsd (129) and C57BL/6JOlaHsd (C57) strains were assessed for performance on a test battery including sensorimotor, affective and cognitive measures, using established as well as modified paradigms. Marked strain differences were observed in measures of locomotion, motor coordination and anxiety: the 129 mice were typically less active and more anxious. In contrast, the strains did not markedly differ in muscular strength, habituation to an open field or spatial working memory. The data provide baseline parameters of behaviour against which genetically modified lines derived from these particular parental strains can be assessed.

Affect↗

Burrowing into prion disease.

Mice received intra-hippocampal injections of scrapie-infected brain homogenate. Open field activity increased from around week 12 post-injection. Concomitantly the tendency to displace food from a tube inside the home cage decreased. The food was generally dug out with the feet, rather than carried by mouth, so its displacement was called burrowing. Food restriction was unnecessary for this burrowing to occur. Only later, around 18 weeks, did more general motor impairments develop. As burrowing in scrapie-infected mice decreased when open field activity increased, and preceded later motor impairments, it was not due to motor dysfunction. Burrowing is a simple, sensitive, objective, ethological measure, sensitive to preclinical prion disease. Other potential applications are in transgenic and knockout mice, models of ageing and Alzheimer's disease, and pharmacology, particularly neuroleptics.

Animals↗

Conditional discriminations based on external and internal cues in rats with cytotoxic hippocampal lesions.

Septal-hippocampal system lesions, mostly using aspiration techniques, have been reported to impair performance of conditional tasks. Rats with axon-sparing cytotoxic hippocampal lesions were therefore tested in a range of instrumental conditional paradigms. They did not differ from controls in their ability to choose the appropriate object in a conditional object discrimination cued by internal state (hunger or thirst) or on performance of conditional visuospatial object discriminations. Acquisition of a conditional visuospatial discrimination with black and white boxes as stimuli was also unimpaired. In contrast, lesioned rats were profoundly impaired on an open T-maze task when cued by either their internal state (reference memory task) or their previous response (working memory task). The results indicate that perception or use of spatial cues, rather than conditional responding per se, is impaired by cytotoxic hippocampal lesions.

Abortion, Habitual↗

Early behavioural changes in scrapie-affected mice and the influence of dapsone.

Behavioural testing can reveal effects in scrapie-infected mice long before overt clinical signs appear (Betmouni et al., 1999, Psychobiology, 27, 63-71). These effects may be partly attributable to an early, atypical inflammatory response in the brain (Betmouni et al., 1996, Neuroscience, 74, 1-5). The present study replicated and extended these findings, and examined the effect of chronic treatment with dapsone. This anti-inflammatory compound has been reported to delay disease onset in a rat model of Creutzfeldt-Jakob disease (Manuelidis et al., 1998, Lancet, 352, 456). Although the doses used in the present study were higher than those of Manuelidis et al. (1998), no attenuation of the disease was seen in either behavioural or subsequent histological tests. Burrowing, i.e. displacing food pellets from a tube in the home cage, decreased from around week 12 in scrapie-infected mice, as did consumption of palatable glucose solution. Concurrently, ambulation in an open field increased, as did rearing at around week 17. Spontaneous alternation was impaired around this time. Around 18 weeks, motor performance on an inverted screen, horizontal bar, rotating rod and static rods decreased. Nest construction was impaired at 20 weeks. Overt clinical signs (reduction in mobility, hunched posture, poor coat condition, bladder enlargement) only occurred after week 20, when the mice were prepared for histology. The ME7 scrapie-infected mice thus showed a characteristic complex of neurological and behavioural changes during the course of the disease that were not ameliorated by dapsone. These changes appeared well before clinical signs were prominent.

Animals↗

Effects of scopolamine on a novel choice serial reaction time task.

Rats were trained on a novel attentional task adapted from the five-choice serial reaction time test first developed by Carli et al. [1983; Behav. Brain. Res., 9, 361-80]. The novel task required rats to detect the occurrence of brief light flashes in one of two spatial locations following trial initiation by a lever press. Blank trials were interleaved with stimulus trials and the rat had to make a different response to indicate the absence of a light. Occasional light-alone trials were also presented in which the visual stimulus appeared without forewarning. Pre-exposure to food for 60 min prior to test increased response omissions for all trials and slowed correct response latency, but failed to significantly alter accuracy. A decrease in light-stimulus duration (1-0.4 s) decreased accuracy, increased the reporting of blank trials and the number of light-alone trial omissions. Scopolamine (0.03-0.1 mg/kg) and scopolamine methylbromide (0.1 mg/kg) failed to affect accuracy, but increased light-alone trial omissions and lengthened correct response latency. The results confirm that the novel task is able to distinguish between motivational and attentional manipulations, and imply that scopolamine affected performance via nonattentional mechanisms.

Animals↗

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↗

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↗

Effects of aspiration lesions of hippocampus or overlying neocortex on concurrent and configural object discriminations in rats.

Rats with aspiration lesions of the hippocampus plus overlying neocortex or control lesions of this cortex alone were trained on five-pair concurrent object discriminations in an enclosed Y-maze and subsequently on an open maze. Acquisition of the former task was impaired only in rats with cortical lesions, but on the latter both groups were equally impaired. Recombining positive and negative stimuli into novel pairs did not disrupt performance. Acquisition of single-pair discriminations was normal or slightly impaired in lesion groups. The cortical, but not the hippocampal group, was impaired on the concurrent learning of a positive and a negative pattern configural task. Recombining stimuli did not impair performance of this task either. The study demonstrates that extensive damage to the hippocampal formation need not necessarily impair concurrent learning, and impairments seen in other studies may relate to details of experimental procedure.

Animals↗

Effects of the competitive NMDA receptor antagonist CGP 37849 on performance of reference and working memory tasks by rats.

The effects of the competitive NMDA receptor antagonist CGP 37849 (DL-(E)-2-amino-4-methyl-5-phosphono-3-pentenoic acid) were tested in rats performing (1) a nonspatial working memory task, and (2) a reference memory task that was either partly or fully learnt. CGP 37849 attenuated accuracy in all three tests, suggesting that sensorimotor effects may obscure any drug effects on memory itself.

2-Amino-5-phosphonovalerate↗

Serial position effects and duration of memory for nonspatial stimuli in rats.

Recognition memory for lists of nonspatial items was tested in rats using a nonmatching-to-sample task. The recency effect at short retention intervals disappeared as the interval increased, but primacy did not develop although responding was still above chance up to 2 hr after 10-s sample times. Neither proactive nor retroactive interference was apparent. Rats transferred the nonmatching-to-sample rule to completely novel stimuli. The study failed to replicate the prominent U-shaped serial position curve found in a similar study by P. Reed, T. Chih-Ta, J.P. Aggleton, and J.N.P. Rawlins (1991), for which E.A. Gaffan and D. Gaffan (1992) had found the data less variable than expected. Evidence of primacy in this procedure remains insubstantial.

Animals↗

Critical determinants of nonspatial working memory deficits in rats with conventional lesions of the hippocampus or fornix.

Rats with conventional lesions of the hippocampus or fornix were compared postoperatively with controls on nonspatial memory tasks. Neither lesion impaired delayed matching-to-sample (DMS) performance in a discrete-trial task involving "pseudo-trial-unique" complex stimuli. An impairment emerged if a single pair of complex stimuli was used throughout each day's session, and the greatest impairment was obtained with the use of a single pair of less complex stimuli throughout each day's test. Transfer to a continuous DMS task with no explicit intertrial interval produced a different pattern because both lesion and control levels of performance were depressed when two complex stimuli were used repeatedly. A final, separate discrimination learning experiment showed that hippocampectomized rats readily discriminated between the stimuli associated with the greatest lesion-induced DMS deficit. Hippocampal dysfunction thus produces clear deficits on non-spatial memory tasks under appropriate test conditions.

Animals↗

Effects of RU33368, a low affinity ligand for neuronal benzodiazepine receptors, on rodent behaviours and GABA-mediated synaptic transmission in rat cerebellar slices.

1. The effects of the low affinity benzodiazepine receptor ligand RU33368 were studied on rodent behaviours and on GABA-mediated synaptic transmission in rat cerebellar slices. 2. RU33368 inhibited stress induced ultrasounds in rat pups without inducing marked muscle relaxation. RU33368 also enhanced operant responding in rats that had been suppressed by mild footshock. These effects of RU33368 in these two models of anxiety were both blocked by the benzodiazepine antagonist Ro15-1788 (flumazonil). 3. In cerebellar slices RU33368 enhanced stimulus-induced synaptic inhibition of Purkinje layer cells with a minimal effective concentration in the order of 1 microM. The classical benzodiazepine agonist RU32007 was approx. 10 times more potent. This action of RU33368 was blocked by Ro15-1788. 4. The minimal effective concentration of RU33368 fully blocked the effect of RU32007 in 2 of 4 cells tested and partially antagonized it in a third cell. 5. These data suggest that RU33368 is a partial agonist at benzodiazepine receptors and this, at least in part, explains its non-sedative anxiolytic behavioural profile.

Animals↗

Differential interactions of Ro 15-4513 with benzodiazepines, ethanol and pentobarbital.

The effects of the imidazobenzodiazepine Ro 15-4513 in combination with three CNS depressants (ethanol, benzodiazepine agonists and pentobarbital) were examined in three different experiments. Full antagonism of classical benzodiazepines by Ro 15-4513 was seen in all three situations. Partial antagonism of ethanol occurred in the pull up test of muscle relaxation in rats, but not in the inhibition of ultrasounds produced in rat pups by mild stress. The depressant effect of ethanol on twitching of the urethane-anaesthetised rat suprahyoid muscles was reversed. No attenuation of the effects of pentobarbital was seen in any test.

Anesthesia↗

The pull-up test in rats: a simple method for evaluating muscle relaxation.

A test for muscle relaxation in rats is described. The pull-up test is performed by holding an inverted rat by its hind legs. The time taken by the rat to pull itself up and grasp the hand of the experimenter is used as the test parameter. It is simple and quick and separates muscle relaxation from sedation, catalepsy, and catatonia.

Animals↗

Effect of naloxone on the behaviour of rats exposed to a novel environment.

It has recently been suggested that endogenous opiates may play a general role in stress responding. To test this hypothesis, naloxone hydrochloride (0.5-4.0 mg/kg SC) was administered to rats exposed to an open field situation. Naloxone treatment produced a decrease in locomotor activity and rearing, and an increase in defaecation. A simple dose-response relationship was not observed, with the most potent effects exerted by the 1 mg/kg dose. Nvertheless, these results indicate that naloxone increases emotionality in the rat and suggest that opioid peptides may be released under conditions of nonpainful stress.

Animals↗