David C.S. Roberts

Bio: David C.S. Roberts is an academic researcher from Wake Forest University. The author has contributed to research in topics: Nucleus accumbens & Dopamine. The author has an hindex of 59, co-authored 154 publications receiving 13005 citations. Previous affiliations of David C.S. Roberts include University of British Columbia & Carleton University.

Extinction and recovery of cocaine self-administration following 6-hydroxydopamine lesions of the nucleus accumbens.

Abstract: The effect of 6-OHDA injections into the nucleus accumbens was examined on cocaine self-administration behaviour. Rats were given access to cocaine (0.75 mg/kg/inj.) for three hours/day on a continuous reinforcement schedule. After daily intake of cocaine had stabilized, rats were injected with 6-OHDA (8 μg/2 μl). When tested the day following the 6-OHDA injection most rats failed to self-administer cocaine, however this disruption did not resemble extinction. After several days self-administration recovered in many animals to near preoperative levels, and the rate of this recovery correlated (r = +0.75) with the levels of dopamine remaining in the nucleus accumbens. The animals with the greatest depletion of dopamine did not recover cocaine intake. In a separate experiment, animals were pretreated with desmethylimipramine and/or pargyline to achieve a more extensive and selective lesion. When tested five days after the lesion all animals in these 6-OHDA groups showed a significant decline in cocaine intake compared to vehicle injected control animals. Several 6-OHDA treated animals displayed a pattern of behaviour resembling extinction, where a high rate of lever pressing was followed by cessation of responding. Some animals were aalso tested for apomorphine self-administration and this was found not to be affected by the 6-OHDA treatment. These data support the hypothesis that non-striatal dopamine may subserve cocaine reward.

On the role of ascending catecholaminergic systems in intravenous self-administration of cocaine.

Abstract: The role of ascending noradrenergic (NA) and dopaminergic (DA) systems in intravenous self-administration of cocaine in rats was investigated by examining the effects of 6-hydroxydopamine-induced lesions of these systems on responding for the drug on a FR-1 schedule of reinforcement. Lesions of the dorsal and ventral NA bundles that reduced hippocampal-cortical NA by 96% and hypothalamic NA by 72% failed to have any effects on responding for cocaine. Lesions of the nucleus accumbens that reduced the DA content of this nucleus by 90% resulted in a significant and long-lasting (15 days) reduction in self-administration of cocaine. Apomorphine self-administration was not affected in the same animals. Identical lesions of the n accumbens had only transient (2-3 days) effects on food-reinforced operant responding, suggesting that the prolonged disruption of cocaine self-administration was not the result of motor deficits. The results are discussed with reference to the possibility that DA terminals in the n accumbens may mediate some of the positive reinforcing properties of cocaine.

Disruption of cocaine self-administration following 6-hydroxydopamine lesions of the ventral tegmental area in rats

Abstract: 6-Hydroxydopamine-induced destruction of dopaminergic terminals in the nucleus accumbens have been shown previously to disrupt cocaine and amphetamine self-administration. We sought to determine whether lesions of the DA cell bodies in the ventral tegmental area (VTA) which give rise to the DA innervation of the n. accumbens, would also disrupt cocaine self-administration behavior. Rats were trained to self-inject cocaine (0.75 mg/kg) for 4 hr/day. After a stable baseline was established, one group of rats received bilateral injections of 6-OHDA (4 micrograms/l microliter) into the VTA. Control rats received vehicle injections. When retested on the fifth day post-lesion, all of the 6-OHDA treated animals showed a long lasting reduction in cocaine intake. Three animals did not reinitiate cocaine self-administration after the lesion, although each showed stable post-lesion responding for apomorphine. The surgery had no effect on cocaine self-administration in control animals. These data support the hypothesis that dopaminergic mechanisms are necessary for the normal expression of cocaine self-administration.

A critique of fixed and progressive ratio schedules used to examine the neural substrates of drug reinforcement.

Abstract: This paper is a critique of fixed and progressive ratio schedules used to examine the neural substrates of cocaine reinforcement. The discussion focuses on problems encountered while examining the effects of neurotoxic lesions and pharmacological pretreatments on cocaine reinforcement. We review the theoretical and interpretational problems associated with the use of the fixed ratio (FR) schedules that have been used in the majority of studies, and we conclude that rate of drug intake cannot directly address the issue of increased or decreased reinforcer efficacy. The progressive ratio (PR) schedule offers some advantages over FR schedules, although it is now clear that the same implementation cannot be applied across all drug classes. It is likely that the motivation to self-administer psychostimulant vs. opiate drugs is qualitatively different. We conclude that there is no single schedule that can quantify all aspects of drug reinforcement and that behavioral paradigms will need to be adapted according to the particular question under study.

Sources of Method Bias in Social Science Research and Recommendations on How to Control It

Abstract: Despite the concern that has been expressed about potential method biases, and the pervasiveness of research settings with the potential to produce them, there is disagreement about whether they really are a problem for researchers in the behavioral sciences. Therefore, the purpose of this review is to explore the current state of knowledge about method biases. First, we explore the meaning of the terms “method” and “method bias” and then we examine whether method biases influence all measures equally. Next, we review the evidence of the effects that method biases have on individual measures and on the covariation between different constructs. Following this, we evaluate the procedural and statistical remedies that have been used to control method biases and provide recommendations for minimizing method bias.

Principles of Neural Science

Abstract: I have developed "tennis elbow" from lugging this book around the past four weeks, but it is worth the pain, the effort, and the aspirin. It is also worth the (relatively speaking) bargain price. Including appendixes, this book contains 894 pages of text. The entire panorama of the neural sciences is surveyed and examined, and it is comprehensive in its scope, from genomes to social behaviors. The editors explicitly state that the book is designed as "an introductory text for students of biology, behavior, and medicine," but it is hard to imagine any audience, interested in any fragment of neuroscience at any level of sophistication, that would not enjoy this book. The editors have done a masterful job of weaving together the biologic, the behavioral, and the clinical sciences into a single tapestry in which everyone from the molecular biologist to the practicing psychiatrist can find and appreciate his or

Précis of The Neuropsychology of Anxiety: An Enquiry into the Functions of the Septo-Hippocampal System..

Abstract: A model of the neuropsychology of anxiety is proposed. The model is based in the first instance upon an analysis of the behavioural effects of the antianxiety drugs (benzodiazepines, barbiturates, and alcohol) in animals. From such psychopharmacologi-cal experiments the concept of a “behavioural inhibition system” (BIS) has been developed. This system responds to novel stimuli or to those associated with punishment or nonreward by inhibiting ongoing behaviour and increasing arousal and attention to the environment. It is activity in the BIS that constitutes anxiety and that is reduced by antianxiety drugs. The effects of the antianxiety drugs in the brain also suggest hypotheses concerning the neural substrate of anxiety. Although the benzodiazepines and barbiturates facilitate the effects of γ-aminobutyrate, this is insufficient to explain their highly specific behavioural effects. Because of similarities between the behavioural effects of certain lesions and those of the antianxiety drugs, it is proposed that these drugs reduce anxiety by impairing the functioning of a widespread neural system including the septo-hippocampal system (SHS), the Papez circuit, the prefrontal cortex, and ascending monoaminergic and cholinergic pathways which innervate these forebrain structures. Analysis of the functions of this system (based on anatomical, physiological, and behavioural data) suggests that it acts as a comparator: it compares predicted to actual sensory events and activates the outputs of the BIS when there is a mismatch or when the predicted event is aversive. Suggestions are made as to the functions of particular pathways within this overall brain system. The resulting theory is applied to the symptoms and treatment of anxiety in man, its relations to depression, and the personality of individuals who are susceptible to anxiety or depression.