Trevor W. Robbins

Bio: Trevor W. Robbins is an academic researcher from University of Cambridge. The author has contributed to research in topics: Prefrontal cortex & Impulsivity. The author has an hindex of 231, co-authored 1137 publications receiving 164437 citations. Previous affiliations of Trevor W. Robbins include Centre national de la recherche scientifique & Massachusetts Institute of Technology.

The novel μ-opioid receptor antagonist GSK1521498 decreases both alcohol seeking and drinking: evidence from a new preclinical model of alcohol seeking

Abstract: Distinct environmental and conditioned stimuli influencing ethanol-associated appetitive and consummatory behaviors may jointly contribute to alcohol addiction. To develop an effective translational animal model that illuminates this interaction, daily seeking responses, maintained by alcohol-associated conditioned stimuli (CSs), need to be dissociated from alcohol drinking behavior. For this, we established a procedure whereby alcohol seeking maintained by alcohol-associated CSs is followed by a period during which rats have the opportunity to drink alcohol. This cue-controlled alcohol-seeking procedure was used to compare the effects of naltrexone and GSK1521498, a novel selective μ-opioid receptor antagonist, on both voluntary alcohol-intake and alcohol-seeking behaviors. Rederived alcohol-preferring, alcohol-nonpreferring, and high-alcohol-drinking replicate 1 line of rats (Indiana University) first received 18 sessions of 24 h home cage access to 10% alcohol and water under a 2-bottle choice procedure. They were trained subsequently to respond instrumentally for access to 15% alcohol under a second-order schedule of reinforcement, in which a prolonged period of alcohol-seeking behavior was maintained by contingent presentations of an alcohol-associated CS acting as a conditioned reinforcer. This seeking period was terminated by 20 min of free alcohol drinking access that achieved significant blood alcohol concentrations. The influence of pretreatment with either naltrexone (0.1-1-3 mg/kg) or GSK1521498 (0.1-1-3 mg/kg) before instrumental sessions was measured on both seeking and drinking behaviors, as well as on drinking in the 2-bottle choice procedure. Naltrexone and GSK1521498 dose-dependently reduced both cue-controlled alcohol seeking and alcohol intake in the instrumental context as well as alcohol intake in the choice procedure. However, GSK1521498 showed significantly greater effectiveness than naltrexone, supporting its potential use for promoting abstinence and preventing relapse in alcohol addiction.

Effects of diazepam, FG 7142, and RO 15-1788 on schedule-induced polydipsia and the temporal control of behavior.

Abstract: Although benzodiazepine agonists and inverse agonists have opposite effects on drinking elicited by water deprivation, there is much less information about the effects of these drugs on nonhomeostatic drinking. In this experiment the effects of diazepam (0.3–5.0 mg/kg), a benzodiazepine receptor agonist, and FG 7142 (1.0–9.0 mg/kg), an inverse agonist, were determined on drinking elicited by a FT-60 schedule of food delivery (SIP). Both diazepam and FG 7142 dose-dependently reduced SIP, measured as either licking or volume consumed. In addition, diazepam reduced panel pressing for food, decreased locomotor activity, and changed the time course of each behavior. In contrast, FG 7142 reduced schedule-induced drinking without significantly altering other behaviors. The antagonist RO 15-1788, when given in combination with these drugs, only partially restored the reductions in licking produced by diazepam, but was much more effective in reversing the effects of FG 7142 at doses of the antagonist that failed by themselves to affect responding. The opposite pattern of effects was seen on the volume of water consumed. These effects are discussed in terms of the behavioral and pharmacological specificity of these drugs.

Lesions of the pedunculopontine tegmental nucleus increase sucrose consumption but do not affect discrimination or contrast effects.

Abstract: Pedunculopontine tegmental nucleus (PPTg) lesions block place preferences to drugs or food only when animals are nondeprived. PPTg lesions also disrupt operant responding, but lesioned rats cannot discriminate active from inactive levers. It is not clear, therefore, whether PPTg lesions block reward or disrupt the ability to differentiate changes in reward magnitude. These hypotheses were tested by measuring sucrose consumption, choice, and contrast effects after PPTg lesions. Both sham and lesioned rats consumed greater amounts of a sucrose solution as the concentration and level of deprivation were increased. Given a choice between 2 solutions, all rats consumed more of the higher concentration. Both groups exhibited contrast effects when the concentration was shifted from 32% to 4% within a session. Somewhat surprisingly, lesions increased sucrose intake when rats were food-restricted. These results suggest that PPTg lesions do not disrupt primary motivation or the ability to evaluate and respond to changes in reward strength.

Disorders of brain and mind

Abstract: Introduction D. F. Benson Part I. Basal Ganglia and Neuropsychiatry: 1. The neuropsychology of basal ganglia disorders: an integrative cognitive and comparative approach T. W. Robbins, A. M. Owen and B. J. Sahakian 2. The behavioural pharmacology of brain dopamine systems: implications for the cognitive pharmacotherapy of schizophrenia E. Joyce and S. Hutton Part II. Frontal Lobes and Neuropsychiatry: 3. The neuropsychology of the frontal lobes S. E. McPherson and J. L. Cummings 4. Frontal lobe structural abnormalities in schizophrenia: evidence from neuroimaging B. Toone Part III. Memory and its Disorders: 5. Neuropsychology of memory and amnesia A. R. Mayes 6. Clinical and neuropsychological studies of patients with amnesic disorders M. D. Kopelman Part IV. Brain Disease and Mental Illness: 7. Psychiatric manifestations of demonstrable brain disease M. A. Ron 8. Structural brain imaging in the psychoses S. Lewis Part V. Epilepsy: Biology and Behaviour: 9. Behaviour in chronic experimental epilepsies J. G. R. Jefferys and J. Mellanby 10. A neurobiological perspective of the behaviour disorders of epilepsy M. R. Trimble Part VI. Perspectives on Neurodevelopment: The Case of Schizophrenia: 11. Early disorders and later schizophrenia: a developmental neuropsychiatric perspective E. Taylor 12. Neurodevelopmental disturbances in the aetiology of schizophrenia J. M. Hollister and T. D. Cannon Part VII. Imaging Brain and Mind: 13. Magnetic resonance spectroscopy in neuropsychiatry M. Maier 14. The hallucination: a disorder of brain and mind A. S. David and G. Busatto.

Cognition in schizophrenia: from basic science to clinical treatment.

Abstract: Interest in cognition in schizophrenia has skyrocketed in the past decade, as evidenced by this special issue. This issue is partially based on presentations made at the 5th Biennial Mount Sinai Conference on Cognition in Schizophrenia, in April 2001 in Whistler, B.C., Canada. The first Mount Sinai Meeting in 1993 had 27 attendees and the one in Whistler (from which this issue originated) had 298. The latest meeting, in Colorado Springs in 2003, had 315 attendees. The number of publications on the topic has increased as well, with some journal editors noting that the majority of papers on schizophrenia submitted to their journals are focused on cognitive functioning. The number of papers on cognition in schizophrenia published and presented at major meetings has increased as much as 5-fold in the past 15 years. Further, the NIH has recently acknowledged (Hyman and Fenton 2003) that treatment of cognitive impairment with pharmacological means is an important intervention target, as evidenced by several recent initiatives that are aimed at the treatment of cognitive impairment in schizophrenia through various means. This increase in interest can be traced to two emerging trends. The first is the increased understanding of the functional importance of cognitive impairments in schizophrenia, where it is now widely accepted, in the scientific if not the clinical community, that cognitive impairments are the primary determinant of functional deficits in schizophrenia (e.g. Green 1996; Harvey et al. 1998; Green et al. 2000). Since functional limitations in the illness are responsible for much of the disability that occurs, this is an important revelation and one that has moved the study of cognition in schizophrenia outside the realm of an academic exercise. The second important trend in the field is the increased interest in the neurobiology and treatment of cognitive impairment in schizophrenia. If cognitive deficits are the determinants of functional limitations, it seems logical that treatment of cognitive deficits would lead, all other things equal, to functional improvements. Treatments can be either behavioral in nature or pharmacologically based. Rational pharmacology will progress the most rapidly with the understanding of biological substrates of cognitive impairments. This Special Issue is multifaceted in its topics. They arise from three different sources, including presentations made at the Mount Sinai conference in 2001, articles spontaneously submitted to the journal that addressed the neural bases of cognitive impairments in schizophrenia, and articles that address basic science topics that are relevant to cognitive impairments similar to those seen in schizophrenia. There are three different sections in this issue. The sections include studies of NMDA receptor manipulations, pharmacological manipulation of prepulse inhibition and latent inhibition, and treatment of cognitive impairments in schizophrenia, with a final article describing the US National Institute of Health’s large-scale project on Measurement and Treatment Research Involving Cognition in Schizophrenia (MATRICS). This project itself arises from the increased recognition of the fact that treating cognition in schizophrenia may be the path to improvement in functional outcome in the illness. While mice are not men and a widely useful animal model of schizophrenia in general has proven difficult to develop, we believe that the usefulness of animal models P. D. Harvey ()) Department of Psychiatry, Mt. Sinai School of Medicine, Box 1229, New York, NY 10029, USA e-mail: pdharvey@compuserve.com

疟原虫var基因转换速率变化导致抗原变异[英]／Paul H, Robert P, Christodoulou Z, et al//Proc Natl Acad Sci U S A

Abstract: 抗原变异可使得多种致病微生物易于逃避宿主免疫应答。表达在感染红细胞表面的恶性疟原虫红细胞表面蛋白1（PfPMP1）与感染红细胞、内皮细胞、树突状细胞以及胎盘的单个或多个受体作用，在黏附及免疫逃避中起关键的作用。每个单倍体基因组var基因家族编码约60种成员，通过启动转录不同的var基因变异体为抗原变异提供了分子基础。

Control of goal-directed and stimulus-driven attention in the brain

Abstract: We review evidence for partially segregated networks of brain areas that carry out different attentional functions. One system, which includes parts of the intraparietal cortex and superior frontal cortex, is involved in preparing and applying goal-directed (top-down) selection for stimuli and responses. This system is also modulated by the detection of stimuli. The other system, which includes the temporoparietal cortex and inferior frontal cortex, and is largely lateralized to the right hemisphere, is not involved in top-down selection. Instead, this system is specialized for the detection of behaviourally relevant stimuli, particularly when they are salient or unexpected. This ventral frontoparietal network works as a 'circuit breaker' for the dorsal system, directing attention to salient events. Both attentional systems interact during normal vision, and both are disrupted in unilateral spatial neglect.

An integrative theory of prefrontal cortex function

Abstract: ▪ Abstract The prefrontal cortex has long been suspected to play an important role in cognitive control, in the ability to orchestrate thought and action in accordance with internal goals. Its neural basis, however, has remained a mystery. Here, we propose that cognitive control stems from the active maintenance of patterns of activity in the prefrontal cortex that represent goals and the means to achieve them. They provide bias signals to other brain structures whose net effect is to guide the flow of activity along neural pathways that establish the proper mappings between inputs, internal states, and outputs needed to perform a given task. We review neurophysiological, neurobiological, neuroimaging, and computational studies that support this theory and discuss its implications as well as further issues to be addressed

Chapter 11 Working memory

Abstract: Publisher Summary This chapter focuses on the modern notion of short-term memory, called working memory. Working memory refers to the temporary maintenance of information that was just experienced or just retrieved from long-term memory but no longer exists in the external environment. These internal representations are short-lived, but can be maintained for longer periods of time through active rehearsal strategies, and can be subjected to various operations that manipulate the information in such a way that makes it useful for goal-directed behavior. Working memory is a system that is critically important in cognition and seems necessary in the course of performing many other cognitive functions, such as reasoning, language comprehension, planning, and spatial processing. This chapter demonstrates the functional importance of dopamine to working memory function in several ways. Elucidation of the cognitive and neural mechanisms underlying human working memory is an important focus of cognitive neuroscience and neurology for much of the past decade. One conclusion that arises from research is that working memory, a faculty that enables temporary storage and manipulation of information in the service of behavioral goals, can be viewed as neither a unitary, nor a dedicated system. Data from numerous neuropsychological and neurophysiological studies in animals and humans demonstrates that a network of brain regions, including the prefrontal cortex, is critical for the active maintenance of internal representations.