Preface

Chapter 8 **Review of Current Neuroimaging Studies of the Effects of**

Richardson

**VI** Contents

**Prenatal Drug Exposure: Brain Structure and Function 193** Jennifer Willford, Conner Smith, Tyler Kuhn, Brady Weber and Gale

> Drug addiction represents a major public health concern. This statement has been echoed at the beginning of many of our papers and presentations over the last 20 years, and we imag‐ ine this has been the same for the majority of our colleagues. Indeed, substance use disor‐ ders have taken and continue to take a major toll on individuals, families, clinicians, and society at large. However, beyond this beginning statement, the majority of this book does not resemble one that might have been written 20 years ago. Technological advances and the findings that have followed from their application have allowed our understanding of drug addiction to progress. Moreover, we are seeing an emphasis on translating our growing knowledge to advances into clinical practice. This book includes eight chapters that not only review the past and present status of various topics related to drug addiction, but also illus‐ trate how our increasing understanding of the neurobiological basis of drug addiction is lay‐ ing the foundation for future clinical approaches that will benefit those suffering from addictive disorders.

> This book opens with a discussion of the neurocircuitry underlying addictive behavior through the lens of evolution. From this unique perspective, Chapter 1 describes the roles of the lateral and medial habenula in modulating the activity of the monoaminergic reward pathways (classically the primary focus of addiction research) and the stress/anxiety path‐ ways (increasingly recognized as central to addiction). The authors present an anatomical model in which the lateral habenula gates reward-seeking depending on the valence of the expected reward, and the medial habenula activates misery-fleeing behavior and dysphoria that accompany drug craving. Consequently, the authors postulate that the habenula has a dual-role in transition to addiction and relapse during abstinence. Chapter 2 continues with epigenetic mechanisms in addiction, a relatively nascent, but intriguing field of study. Epi‐ genetic modifications, such as DNA methylation, histone modification, and non-coding RNAs, induce long-lasting, even intergenerational, changes in gene expression and are thus poised to contribute uniquely to the relapsing nature of addiction. Although studies to date have focused primarily on alcohol and cocaine, evidence that epigenetic modifications medi‐ ate many of the persistent molecular changes in the brain occurring with repeated drug ex‐ posure, or life experiences that confer risk for addiction (such as stress), is compelling.

> Chapter 3 summarizes the commonly used rodent models of alcohol intake and seeking be‐ havior and discusses how they have combined with recent methodological advances to re‐ veal neurobiological substrate regulating aspects of alcohol use disorders. The authors present the strengths and limitations of drinking paradigms as well as operant self-adminis‐ tration and place conditioning, which reflect the importance of environmental cues in re‐ lapse. Chapter 3 then describes the classical and modern techniques used to elucidate the molecular mechanisms and neural structures that mediate alcohol-related behavior. Finally, the authors discuss some key findings in the alcohol research field made possible by these approaches. Chapter 4 further develops the well-established role of dopaminergic signaling

in alcohol drinking and reward. It reviews the efficacy and tolerability of pharmacological treatments targeting dopamine transmission and suggests that newer agents that stabilize or indirectly modulate the mesolimbic dopamine system may be superior therapies, reflecting the paradigm shift from potent selective pharmaceuticals to more moderate approaches that target drug reward with fewer side effects. Chapter 5 further illustrates how our under‐ standing of addiction now extends well beyond the mesolimbic dopamine system. This chapter highlights how dysregulation of serotonin and noradrenaline within the basolateral amygdala results in stress-induced negative emotional states upon alcohol withdrawal and subsequent craving and vulnerability to relapse. The potential of several putative pharmaco‐ therapies for alcohol use disorders that target these transmitter systems are addressed.

Despite being endorsed by the majority of psychological and medical organizations, the medical or disease model of drug addiction remains overshadowed by the view that drug addiction represents a moral failing among wide swaths of the population. The continued controversy surrounding these theoretical perspectives can be seen across Chapter 6, which provides an overview of major approaches to treating substance use disorders, outlining their origins and core features. Moreover, this chapter provides the reader with a platform to consider advances in clinical practices, the importance of evidence-based approaches to treating addiction, and considers how drug courts may represent a potential reconciliation of the medical and moral approaches to addressing substance use disorders. The value of appreciating the dynamic nature of factors related to the development of drug addiction is well illustrated in Chapter 7, which compares two cohorts of dual diagnosis patients admit‐ ted to an acute psychiatry ward 10 years apart. This chapter highlights that while our cur‐ rent knowledge of substance use disorders can be informed by past research, we cannot solely rely on our previous understanding as a variety of changing demographic, societal, and pharmacological influences can shape the nature of problems faced by addicts and healthcare professionals alike. Chapter 8 reviews recent neuroimaging studies examining the effects of prenatal exposure across of a variety of addictive drugs on brain structure, function, developmental trajectory, and behavior. While emphasizing the challenges associ‐ ated with research examining the effects of prenatal drug exposure this chapter also raises the possibilities that biomarkers will emerge that might ultimately inform prevention and intervention programs.

Perhaps believing we will one day be saying that drug addiction is no longer a major public health concern is both optimistic and unrealistic? It is our hope that in coming decades we will see many of the ideas and translational approaches articulated here come to fruition and the next wave of technological advances will build upon our cumulative understanding of addictive processes and reduce the suffering of those directly and indirectly impacted by substance use disorders.

> **William M. Meil Ph.D.** Professor of Psychology Indiana University of Pennsylvania

> **Christina L. Ruby Ph.D.** Assistant Professor of Biology Indiana University of Pennsylvania
