Papers by Neil McNaughton
Journal of Psychopharmacology, 1991
The effects of buspirone were tested on rearing in an open field. Six different doses of buspiron... more The effects of buspirone were tested on rearing in an open field. Six different doses of buspirone (10, 3.3, 1.1, 0.3, 0.1 and 0.04 mg/kg) and a single dose of chlordiazepoxide (5 mg/kg) were administered i.p. to separate groups of rats. Buspirone produced a dose-dependent decrease in rearing in the range 0.04-10 mg/kg, whereas only the higher doses (10 and 3.3 mg/kg) decreased ambulation significantly. Chlordiazepoxide reduced rearing to an extent equivalent to 1 mg/kg of buspirone. Together with data in the literature, the results suggest that 5-HT1A agonists affect rearing at lower doses than ambulation; that the effects of buspirone in the open field are similar to classical anxiolytics; and that changes in rearing may be more closely related to anxiolytic than muscle relaxant, anti-convulsant and other GABA-mediated effects of the classical anxiolytics.
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Hippocampus, 1995
We have previously shown that in urethane-anesthetized rats the frequency of rhythmical slow acti... more We have previously shown that in urethane-anesthetized rats the frequency of rhythmical slow activity in the hippocampus ("theta") is controlled by the medial supramammillary nucleus (SuM). In particular, injections of procaine into SuM in urethane-anesthetized animals reduce the frequency of theta. However, it has been reported that, in freely moving animals, lesions of SuM do not affect theta. The present experiments were designed to resolve this anomaly. Injections of procaine or chlordiazepoxide into SuM in urethane-anesthetized animals reduced the frequency of theta elicited by reticular stimulation. Mapping showed that procaine injections in freely moving animals were effective in the same locations as under urethane anesthesia. Injections of chlordiazepoxide were effective in a more restricted area than procaine, consistent with an action on synapses in SuM and sparing fibers afferent to SuM. Analysis of the functional spread indicated an effective radius of diffusion of the drugs of 500 microns. With optimal placements, this implied an action on at least 80% of SuM. However, in contrast to the results under urethane, the maximal frequency reductions obtained were less than 50% of the theoretical maximum. In a number of animals receiving repeated injections into SuM, lesions developed which encompassed the whole of SuM. As previously reported, theta was largely intact in SuM-lesioned animals. However, the frequency of theta produced by reticular stimulation was reduced after lesion by approximately the same amount as by procaine injections before lesion. These results suggest that in freely moving animals SuM is only one of two or more nuclei which jointly control the frequency of reticular-elicited theta.
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Journal of Psychopharmacology, 1991
Buspirone is a novel anxiolytic which does not share the muscle relaxant, anticonvulsant and seda... more Buspirone is a novel anxiolytic which does not share the muscle relaxant, anticonvulsant and sedative properties of classical anxiolytics such as the benzodiazepines. Its effects in different animal models of anxiety are also variable. The present experiments investigated the effects of buspirone on a fixed interval 60 s schedule of reinforcement (FI). In experiment 1, four doses of buspirone (10, 3.3, 1.1 and 0.3 mg/kg, i.p.) and two doses of chlordiazepoxide (5 and 20 mg/kg, i.p.) were administered to separate groups of rats throughout acquisition of the FI task. In experiment 2, four doses of buspirone (1.1, 0.3, 0.1 and 0.03 mg/kg, i.p.) and a single dose of chlordiazepoxide (5 mg/kg, i.p.) were used. Chlordiazepoxide generally released responding. At higher doses (1.1 mg/kg and above) buspirone suppressed responding in the later parts of the FI interval. The effects of lower doses were variable but included some response release in the later parts of the FI interval. At no dose did buspirone release responding at the beginning of the FI interval. The experiments show that buspirone differs qualitatively as well as quantitatively from chlordiazepoxide and that current animal models based on behavioural inhibition may need to be used with considerable care if detection of novel anxiolytics is to be ensured.
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Pharmacology Biochemistry and Behavior, 1996
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Leptin has been shown to affect energy homeostasis, learning and memory, and some models of anxio... more Leptin has been shown to affect energy homeostasis, learning and memory, and some models of anxiolytic action. However, leptin has produced inconsistent results in previous non-operant behavioural tests of anxiety. Here, we test the anxiolytic potential of leptin in an operant paradigm that has produced positive results across all classes of anxiolytic so far tested. Rats were tested in the Fixed Interval 60 Seconds (FI60) task following administration of 0/0.5/1.0 mg/kg (i.p.) leptin or an active anxiolytic control of 5 mg/kg (i.p.) chlordiazepoxide (CDP). By the end of the 14 days of testing in the FI60 task, 0.5 mg/kg leptin released suppressed responding in a manner similar to CDP, and 1.0 mg/kg leptin produced a relative depression in responding, a similar outcome pattern to previously tested 5HT-agonist anxiolytics. This suggests that leptin behaves similarly to established serotonergic anxiolytics such as buspirone and fluoxetine; with the delay in development of effect during testing, and the inverted-U dose–response curve explaining the inconsistent behaviour of leptin in behavioural tests of anxiety, as this type of pattern is common to serotonergic anxiolytics.
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Behavioral and Brain Sciences, Sep 1, 1994
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Series in Anxiety and Related Disorders, 2000
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Nature Medicine, Nov 1, 1999
ABSTRACT A partial impairment of GABAA receptor function in mice causes behavioral changes that r... more ABSTRACT A partial impairment of GABAA receptor function in mice causes behavioral changes that resemble generalized anxiety disorder in humans. But understanding the genetic control of the 'neurotic' personality is still a challenge.
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ABSTRACT
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Handbook of Behavioral Neuroscience, 2008
ABSTRACT Theory influences what we mean by the word “anxiety”, what we require of any animal mode... more ABSTRACT Theory influences what we mean by the word “anxiety”, what we require of any animal model, and what specific theoretical constructs are embedded in any specific animal model of anxiety. We argue that, in the ideal case, the animal models we use should be embedded in a large-scale theory that integrates all of the theoretical levels of each animal model. We argue that face validity of a model should be ignored and that true predictive validity reduces ultimately to construct validity. So all models should aim to have construct validity based on strong theory. Theoretical analysis shows that anxiety should be distinguished from fear; that different anxiety disorders should be distinguished from each other; and that the components of any single apparent type of anxiety can have distinct neural control. Theory can show how a model is unsatisfactory, but it can also show that it is not the model but rather our translation from the clinical situation that is faulty. To model the many flavors of clinical disorder and variations in drug effectiveness, we must use theory to link multiple animal models, neural analysis and pharmacological analysis. The goal is to provide us with truly predictive tests that can be used for drug discovery as well as drug development. Most importantly, theory is required if we are to correctly match a particular measure from a particular model with the clinical entity we desire to model.
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Concepts of Long-term Potentiation and Beyond, 2000
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Biology and emotion, 1989
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Biology and emotion, 1989
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Biology and emotion, 1989
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Biology and emotion, 1989
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The Journal of neuroscience : the official journal of the Society for Neuroscience, Jan 15, 2000
Lesion studies show that the hippocampus is critically involved in timing behavior, but so far th... more Lesion studies show that the hippocampus is critically involved in timing behavior, but so far there has been little analysis of how it might encode time. We recorded the activity of 266 CA1 neurons, 51 CA3 neurons, and 219 entorhinal neurons from rats performing on a differential reinforcement of low rates (DRL) 15 sec schedule in which reinforcement was contingent on responses that occurred at least 15 sec after the preceding response. The unit data were analyzed using two different methods. First, each unit was subjected to an ANOVA that examined the effects of the following: (1) the outcome of the previous response (reward or nonreward); (2) the outcome of the response on which the firing of the cell was synchronized; and (3) time. This showed that, for CA1, CA3, and entorhinal cortex, changes in unit activity were related to all aspects of the task, with the firing of >90% of units recorded in each region being related to at least one of the three factors. Second, intercorre...
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Papers by Neil McNaughton