Paul Willner

The behavioural pharmacology of dementia

Almost 50 million individuals live with dementia, worldwide, at an estimated cost of almost a trillion dollars. In recent years, research has clarified many molecular, ultrastuctural and neurodegenerative processes underlying dementia. Unfortunately, however, this solid progress in understanding the neurobiology of dementia has not as yet been matched by advances in treatment, which still rests largely on the use of drugs that potentiate cholinergic activity in the central nervous system. Such treatments can only slow the symptomatic progress of the disease; they neither ameliorate nor inhibit the underlying pathology.

The behavioural pharmacology of stress

Stress is recognized as a major factor in the etiology of psychiatric disorders, yet the interplay between stress and behaviour that contributes to such illnesses remains poorly understood. What determines the wide variety of presentations of stress-related disorders? How do environmental stressors interact with genetic and developmental factors? What are the critical features that determine the perceived intensity of stressors? To what extent are different stressors (e.g. social and physical) equivalent in their effects, and why? To what extent are the numerous animal models of stress interchangeable? These big questions do not even touch upon the underlying brain mechanisms. This Special Issue does not attempt to offer a comprehensive account of the behavioural pharmacology of stress or, indeed, to provide a complete answer to any of these questions, but the 11 reviews and 10 empirical papers included do present a wealth of ideas and data that offer direction and, in some cases, partial answers to many of them.

Behavioural pharmacology of impulse control.

Impulsivity is defined in one of the papers included in this Special Issue as ‘a human behaviour characterized by the inclination of an individual to act on urge rather than thought, with diminished regard to consequences’. Impulsivity is multidimensional in nature, with a distinction often drawn between impulsive action, where rapid responses to situations lead to adverse consequences that could have been avoided by withholding the prepotent response, and impulsive choice where a less beneficial outcome is preferred to a more beneficial outcome that is longer delayed or less certain. Disordered impulse control is a major feature (in some cases, the central feature) of many psychiatric disorders, including addiction to drugs or alcohol, Attention-deficit hyperactivity disorder (ADHD), obsessive–compulsive disorder, obesity, gambling, aggression and self-harm. This has given rise to animal models addressing both impulsive action and impulsive choice. An interesting and to some extent unusual feature of animal models in this area is that very similar procedures can be used to study impulsivity in animals and in humans. This is true of both impulsive action (for example, multichoice serial reaction time tasks) and impulsive choice (e.g. temporal discounting tasks). The use of these homologous animal models has provided insights into the neural substrates of impulsivity, which include a major focus on neurochemical (particularly, dopamine) systems in the ventral striatum and prefrontal cortex in, respectively, promoting and inhibiting impulsivity. There is a striking overlap between these foci and those of addiction research, which is hardly surprising considering the central role of impulsivity in addictions.

Pharmacological approaches to the study of social behaviour.

This Special Issue marks a new departure for Behavioural Pharmacology. Special Issues have always been a feature of this journal, appearing as a double issue every year since Volume 1 in 1990. This year, after dedicating a double Special Issue to the memory of Lex Cools (The behavioural pharmacology of the basal ganglia, Behavioural Pharmacology 26:1–2), the editors announced a second Special Issue showcasing new developments in the pharmacology of social behaviour, anticipating that we would receive sufficient papers to comfortably fill a single issue. We had not anticipated the overwhelming response that resulted in not a single, not a double, but a triple issue, which will be published as Volume 26, Issues 6, 7 and 8. The current issue (Part 1: Issue 26.6) contains eight review papers providing overviews of literature relating to social communication, models of autism, effects of drugs of abuse on social behaviour (and vice versa), and the pharmacology of sexual and maternal behaviour. Parts 2 (Issue 26.7) and 3 (Issue 26.8) will contain empirical studies of the two faces of sociopharmacology: social modulation of drug effects and drug effects on social behaviour. The papers to be included in Parts 2 and 3, and introduced below, are available online in the Behavioural Pharmacology ‘published ahead of print’ pipeline, which may be found at: http://journals.lww. com/behaviouralpharm/toc/publishahead.

The behavioural pharmacology of the basal ganglia : in memory of Lex Cools

Attention-deficit/hyperactivity disorder (ADHD) is accompanied by impairments in cognitive control, such as task-switching deficits. We investigated whether such problems, and their remediation by medication, reflect abnormal reward motivation and associated striatal dopamine transmission in ADHD. We used functional genetic neuroimaging to assess the effects of dopaminergic medication and reward motivation on task-switching and striatal BOLD signal in 23 adults with ADHD, ON and OFF methylphenidate, and 26 healthy controls. Critically, we took into account interindividual variability in striatal dopamine by exploiting a common genetic polymorphism (3-UTR VNTR) in the DAT1 gene coding for the dopamine transporter. The results showed a highly significant group by genotype interaction in the striatum. This was because a subgroup of patients with ADHD showed markedly exaggerated effects of reward on the striatal BOLD signal during task-switching when they were OFF their dopaminergic medication. Specifically, patients carrying the 9R allele showed a greater striatal signal than healthy controls carrying this allele, whereas no effect of diagnosis was observed in 10R homozygotes. Aberrant striatal responses were normalized when 9R-carrying patients with ADHD were ON medication. These pilot data indicate an important role for aberrant reward motivation, striatal dopamine and interindividual genetic differences in cognitive processes in adult ADHD. Copyright (C) 2015 Wolters Kluwer Health, Inc. All rights reserved.

Current approaches to the laboratory assessment of abuse potential.

It has been more than 70 years since Spragg showed that a morphine-dependent chimpanzee would actively seek experimenter-delivered injections of morphine rather than food, and approximately 50 years since pioneering work by Weeks and by Thompson and Schuster showed that morphine-dependent rats and monkeys would press a lever to self-administer morphine through indwelling intravenous catheters. These early demonstrations of the reinforcing effects of morphine in morphine-dependent subjects were quickly followed by an outpouring of selfadministration studies showing that physical dependence was not a necessary pre-condition for drug reinforcement and also documenting the reinforcing effects of CNS drugs from other pharmacological classes, such as barbiturates, ethanol and monoaminergic stimulants. The importance of this early wave of self-administration research was profound. Evidence of the reinforcing effects of drugs in laboratory animals forced both a dramatic change in the general understanding of drug addiction and a new appreciation of the close relationship between the reinforcing properties of a drug and its abuse potential. In turn, these developments contributed to the creation of regulatory agencies in many countries to control access to drugs with abuse potential. For example, the Controlled Substances Act was enacted in 1980 to regulate all aspects of drug production, use, and distribution in the United States, and commanded the classification of known and novel psychoactive drugs into one of five schedules of controlled substances. Secondarily, these developments also highlighted the need for methodology with which to assess the abuse potential of drugs and, thereby, provide essential evidence to the regulatory agencies charged with controlling their availability. The intent of this Special Issue is to describe the status of such methodology, identifying strengths of current laboratory procedures as well as recent conceptual and experimental advances toward the assessment of a drug’s abuse potential.

Pharmacological approaches to feeding behaviour and eating disorders.

The aim of this Special Issue is to explore the contribution that behavioural pharmacology can make to understanding both the mechanisms controlling food intake and feeding behaviour, and the management and treatment of eating disorders. Unlike the newly-emergent topics addressed in some recent Behavioural Pharmacology Special Issues, the pharmacology of feeding behaviour has a venerable history and was a major area of early research in behavioural pharmacology. After some decades of lesser prominence, this area has again come into sharp focus for behavioural pharmacologists through research into newly-discovered neurochemical systems such as cannabinoids and orexins, which have major non-motoric influences on food intake. These developments parallel the increasing public alarm concerning eating disorders and obesity, the prevalence of which has reached crisis proportions (in some reports, estimated to affect around a third of adults in the USA, and over 500 million people worldwide), and creating a health time bomb that has the potential to overwhelm services.

Announcement of 2013 Special Issue: Current Approaches to the Laboratory Assessment of Abuse Potential

In the nearly 50 years since their introduction, drug self administration procedures have become a highly respected means for investigating the abuse liability of recreational drugs, and for assessing the abuse potential of novel CNS pharmaceuticals. Over this time, selfadministration methodology for assessing abuse potential has evolved to include examination of varying aspects of reinforcement, including the measurement of reinforcing strength using progressive ratio or choice procedures and behavioural economics, as well as the study of relapse-related behaviour using reinstatement procedures. However, drug self-administration methodology is technically arduous and there is constant evaluation of alternative means for accurately measuring abuse potential – particularly in rodent species. With these considerations in mind, we are pleased to announce that the topic of the 2013 Special Issue of Behavioural Pharmacology will be Current Approaches to the Laboratory Assessment of Abuse Potential. This Special Issue is intended to provide the reader with, first, an understanding of the contemporary application of traditional self-administration procedures in the assessment of abuse potential and the challenges presented in the evaluation of drugs from classical and new pharmacological classes and, second, insight into other laboratory approaches that can be used to evaluate abuse potential.

Stimulus properties of drugs and the behavioural pharmacology of pain: in memory of Francis Colpaert

Francis Colpaert, who died in 2010 at the tragically early age of 59, was a founder member of the Editorial Board of Behavioural Pharmacology, and was President of the European Behavioural Pharmacology Society at the time when Behavioural Pharmacology was adopted as the official journal of the Society. Francis Colpaert made major scientific contributions in two main areas: the stimulus properties of drugs, as explored through drug discrimination procedures and the phenomenon of statedependent learning, and the pharmacology of pain, with particular reference to the development of tolerance to the effects of analgesic drugs. On learning of his untimely death, the Editors of Behavioural Pharmacology immediately decided to place earlier plans for the 2011 Special Issue on hold, and instead to focus this Special Issue on these two areas of research.

Announcement of 2011 special issue: pharmacological approaches to the study of social behaviour

Social behaviour is an integral part of the behavioural repertoire of mammals. It is essential for survival, and many psychiatric disorders are associated with social dysfunctions. Therefore, we are happy to announce that the topic of the 2015 Special Issue of Behavioural Pharmacology will be social behaviour, in its widest sense. This includes: intraspecies aggression and social hierarchies; sexual, parental, affiliative and cooperative behaviours; social investigation and recognition; and social play behaviour and social development. Some of these behaviours represent very traditional areas of research interest within behavioural pharmacology (e.g. aggressive and sexual behaviours), whereas others (e.g. affiliative behaviours; social recognition) have attracted more recent interest. Relevant approaches include: drug influences on social behaviour; modulation of drug effects by social interactions; and the neuropharmacological basis of these phenomena. This Special Issue is intended to provide a showcase for research across a broad spectrum of topic areas, including studies involving both animal and human subjects.