Experimental and clinical psychopharmacology: National Institute on Drug Abuse's clinical research agenda.

Studies of drugs and behavior are a core component of virtually every portfolio within the broad purview of the National Institute on Drug Abuse (NIDA). Moreover, psychopharmacological research is an important vehicle for advancing understanding of how drugs of abuse produce their effects, particularly including addiction. However, as with all major public health issues, simply understanding the issue is not enough. NIDA's psychopharmacology projects, therefore, span basic, clinical, and applied (e.g., medication development) research activities. These include the establishment of a nationwide clinical trials network designed to provide an infrastructure to test both behavioral and psychopharmacological treatments in a real-life practice setting with diverse patients. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

A behavioral economic analysis of the relative persistence of behavior: Comment on Meisch (2000).

This commentary examines and reinterprets the concept of relative persistence in drug self-administration studies, described by R. A. Meisch (see record 2000-00465-009), in behavioral economic terms. Over the past several years, investigators in the behavioral sciences have successfully applied consumer demand theory to the study of drug abuse and addiction. The economic concept of demand elasticity (i.e., the changes in the amount of a commodity demanded as a function of changes in price) and the concept of unit price are described in detail, and this commentary shows these concepts provide an alternative interpretation to the relative persistence of behavior. The application of the behavioral economic approach to understanding abuse potential of putative drugs of abuse, in development of medications for drug addiction and in characterizing the transition from drug use to drug addiction, is discussed. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Why psychologists should treat alcohol and drug problems.

Because of the prevalence of substance abuse in general clinical populations, it is important for psychologists to have knowledge and skill in this area. Psychologists also have special expertise to offer in the assessment and treatment of alcohol/drug problems. Current evidence indicates that (1) alcohol/drug problems generally obey ordinary behavioral principles and processes, (2) substance abuse frequently occurs within a broader cluster of psychological problems, (3) the treatment approaches most strongly supported by outcome research are fundamentally psychological in nature, (4) cognitive–behavioral principles are of demonstrable value in motivating change in alcohol/drug use, and (5) clinical skills and styles (e.g., empathy) commonly included in the training of psychologists are important determinants of favorable treatment out comes with substance use disorders. These factors in the context of changing health care indicate that psychologists should play an increasing role in assessing and treating addictive behaviors. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Molecular and cellular basis of addiction

Drug addiction results from adaptations in specific brain neurons caused by repeated exposure to a drug of abuse. These adaptations combine to produce the complex behaviors that define an addicted state. Progress is being made in identifying such time-dependent, drug-induced adaptations and relating them to specific behavioral features of addiction. Current research needs to understand the types of adaptations that underlie the particularly long-lived aspects of addiction, such as drug craving and relapse, and to identify specific genes that contribute to individual differences in vulnerability to addiction. Understanding the molecular and cellular basis of addictive states will lead to major changes in how addiction is viewed and ultimately treated.     

Does habituation play a role in drug habit? Comment on McSweeney, Murphy, and Kowal (2005).

Comment on the article, "Regulation of Drug Taking by Sensitization and Habituation," by McSweeney, et al (see record 2005-10634-001). McSweeney, Murphy, and Kowal offer the intriguing suggestion that the basic behavioral processes of habituation and sensitization play an important role in drug taking, specifically, repeated drug taking. The suggestion is noteworthy because, if correct, it, as the authors point out, could lead to new approaches to prevention and treatment, approaches that involve the use of environmental variables that are relatively accessible. I think their exposition raises several issues. A number of these questions are related to the phenomenon of drug tolerance, an outcome that can be understood as either an instance of or deriving from the process of habituation. The presentation also contains passages in which the logic is not fully clear. Another issue I have with the article is the overall logic approach on the basis of features of drug addiction. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Addiction is a brain disease, and it matters

Scientific advances over the past 20 years have shown that drug addiction is a chronic, relapsing disease that results from the prolonged effects of drugs on the brain. As with many other brain diseases, addiction has embedded behavioral and social-context aspects that are important parts of the disorder itself. Therefore, the most effective treatment approaches will include biological, behavioral, and social-context components. Recognizing addiction as a chronic, relapsing brain disorder characterized by compulsive drug seeking and use can impact society's overall health and social policy strategies and help diminish the health and social costs associated with drug abuse and addiction.     

The value of nonhuman primates in drug abuse research.

The use of nonhuman primates (NHP) is invaluable for drug abuse research. The laboratory animals most closely related to humans are NHP. The phylogeny, anatomy, physiology, neurochemistry, and behavior of NHP are more similar to humans than other laboratory species. There is now an extensive body of literature documenting the neuroanatomical, neurochemical, and neuropharmacological similarities between NHP and humans and the differences between NHP and other laboratory species in dopamine, norepinephrine, serotonin, opioid, and gamma aminobutyric acid systems. Comprehensive studies comparing pharmacokinetics in humans, monkeys, dogs, and rats have shown that data in monkeys are the most predictive of human pharmacokinetic parameters. The long life span and extended adolescent period for NHP permits intensive, long-term investigations and the use of within-subject experimental designs similar to those used in human laboratory studies. Within-subject designs require fewer subjects than standard between-group designs and permit the careful evaluation of individual differences. NHP have been used extensively in drug abuse research for over 40 years and have provided useful information on the behavioral processes associated with drug abuse and addiction as well as drug abuse liability in humans. This review focuses on important species differences between rodents and NHP and on the value of NHP in bridging the gap between rodents and humans to enhance the ability to generalize preclinical findings to human drug abuse. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Impulsivity as a mediating mechanism between early-life adversity and addiction: Theoretical comment on Lovic et al. (2011).

Early-life adversity, impulsivity, and dopaminergic function have all been implicated in adult drug addiction. The article by Lovic, Keen, Fletcher, and Fleming in this issue further elucidates this relationship by demonstrating that early-life adversity can increase impulsivity and decrease behavioral flexibility in adulthood. Recent literature suggests that these results are likely due to structural and functional changes in regions such as the orbitofrontal cortex (OFC) and nucleus accumbens (NAc), as well as altered dopamine activity. Impulsivity and behavioral inflexibility can increase susceptibility to addiction, and in turn, chronic substance abuse can impair the neurocircuitry underlying behavioral inhibition. Thus, early-life adversity may act as an entry point into a feed-forward spiral of impulsivity and addiction via the dysfunction of regions such as the OFC, NAc, and mesolimbic dopamine. (PsycINFO Database Record (c) 2011 APA, all rights reserved)     

Sex differences in vulnerability to drug self-administration.

Recent evidence from both human and animal studies indicates that there are sex differences in all phases of the addiction process, including initiation and acquisition of use, patterns and levels of use, the progression to addiction, and relapse. This brief review summarizes a series of studies on sex differences in drug self-administration in rats on which the Wyeth Young Psychopharmacologist Award was based and relates these findings to human clinical data. Briefly, preclinical findings show that female rats acquire drug self-administration at a faster rate, work harder to obtain drug infusions, "binge" for longer initial periods of time and show a more diurnally dysregulated pattern of self-administration under extended-access conditions, and respond at higher levels under reinstatement testing conditions compared with male rats. Similar results have been reported in humans, suggesting a biological basis of sex differences in vulnerability to drug abuse. A number of biological mechanisms have been explored, and the results show that ovarian hormones play a critical role in modulating the reinforcing effects of drugs of abuse in females. Preclinical studies, in conjunction with human studies, should further inform a sex-specific model for differences in drug abuse, and such a model may be useful for developing prevention and treatment strategies for drug abuse. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Alcohol abuse as molar choice: An update of a 1982 proposal.

This article updates a 1982 article (R. E. Vuchinich, 1982) in which an analysis of alcohol abuse that was based on molar behavioral theories of choice was proposed. The original article and subsequent developments in the addiction literature that are related to the choice perspective are summarized. The molar choice view has been incorporated into human and animal research on addictive behaviors other than alcohol abuse, but it has had little impact on the alcohol literature. This lack of influence on alcohol research is attributed to its poor fit with the Zeitgeist of the relevant scientific community rather than to a lack of potential for positive contributions. This tension with the Zeitgeist is created by the contrast between molecular and molar approaches to studying alcohol abuse. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Mesolimbic dopaminergic decline after cannabinoid withdrawal

The mesolimbic dopamine system has recently been implicated in the long-term aversive consequences of withdrawal from major drugs of abuse. In the present study we sought to determine whether mesolimbic dopamine neurons are involved in the neurobiologic mechanisms underlying withdrawal from chronic cannabinoid exposure. Rats were treated chronically with the major psychoactive ingredient of hashish and marijuana, Delta9-tetrahydrocannabinol (Delta9-THC). Administration of the cannabinoid antagonist SR 141716A precipitated an intense behavioral withdrawal syndrome, whereas abrupt Delta9-THC suspension failed to produce overt signs of abstinence. In contrast, both groups showed a reduction in dopamine cells activity as indicated by extracellular single unit recordings from antidromically identified meso-accumbens dopamine neurons. The administration of Delta9-THC to spontaneously withdrawn rats restored neuronal activity. Conversely, SR 141716A produced a further decrease of spontaneous activity in cannabinoid-treated although it was ineffective in control rats. These data indicate that withdrawal from chronic cannabinoid administration is associated with reduced dopaminergic transmission in the limbic system, similar to that observed with other addictive drugs; these changes in neuronal plasticity may play a role in drug craving and relapse into drug addiction.     

Review of Behavioral analysis of drug dependence.

Reviews the book, Behavioral analysis of drug dependence edited by Steven R. Goldberg and Ian P. Stolerman (1986). This volume brings together the main findings of basic research in behavioral pharmacology that have direct relevance to issues in drug dependence. As the editors note, the book is unique in being organized around behavioral principles rather than specific drug classes. It is also unique in making accessible a series of clearly written, well-edited summaries of the experimental literature to professionals and students who have no special background in behavioral pharmacology. I would recommend the Goldberg and Stolerman collection to researchers as well as substance abuse professionals and I think any student of substance abuse will find much of value here. The book will make a wonderful seminar at the graduate or advanced undergraduate level. Goldberg and Stolerman have succeeded in making an excellent overview of the behavioral pharmacology literature on drug dependence available to us in a single volume. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Specific cue reactivity on computer game-related cues in excessive gamers.

It has been posited that excessive computer game playing behavior, referred to as computer game addiction, meets criteria that have been internationally established to define drug addiction. Nevertheless, there have been no psychophysiological investigations of the underlying mechanisms available to support the characterization of excessive computer gaming as behavioral addiction. To investigate whether excessive computer gaming parallels learning processes in development and maintenance (which are assumed to underlie drug addiction), the authors obtained a psychophysiological assessment of the (learned) emotional processing of computer game-relevant and -irrelevant cues. For this purpose, electroencephalographic recordings in excessive and casual computer game players were conducted. Significant between-group differences in event-related potentials evoked by computer game related-cues were found at parietal regions and point to an increased emotional processing of these cues in excessive pathological players compared with casual players. These results are in concordance with the suggestion that addiction is characterized and maintained through sensitization of the mesolimbic dopaminergic system along with incentive salience of specific addiction-associated cues. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Regulation of Drug Taking by Sensitization and Habituation.

The authors argue that drug taking is an operant behavior that is reinforced by the drug itself. The effectiveness of a drug as a reinforcer is modulated by sensitization and habituation to the drug as it is consumed. According to this model, drug taking stops when habituation reduces the ability of the drug to reinforce its own consumption. Drug taking resumes when spontaneous recovery restores the effectiveness of the drug as a reinforcer. This parsimonious model provides a framework for understanding many findings in the drug literature, including acute and chronic tolerance, the effect of deprivation on consumption, the contextual specificity of tolerance, polydrug abuse, cross-sensitization between stress and drugs, behavioral sensitization, priming, and reinstatement. Although this model cannot explain all aspects of drug taking (e.g., the effect of cognitive manipulations), it has many implications for understanding and controlling human drug consumption and addiction. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Distinguished scientific award for the application of psychology: Charles R. Schuster.

The Distinguished Scientific Award for the Applications of Psychology is presented to a person who has made distinguished theoretical or empirical advances leading to the understanding or amelioration of important practical problems. The 1992 winner is Charles R. Schuster. Schuster was chosen for outstanding contributions and leadership in behavioral pharmacology and drug abuse research. He creatively applied concepts and methods from the experimental analysis of behavior to the study of drugs of abuse and was a pioneer in the use of human subjects for behavioral pharmacology research. In addition, his innovative studies of tolerance led to a worldwide appreciation for the role of learning in adaption to repeated drug use. A biography for Schuster is presented, along with a selected bibliography of his work. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Narp regulates long-term aversive effects of morphine withdrawal.

Although long-lasting effects of drug withdrawal are thought to play a key role in motivating continued drug use, the mechanisms mediating this type of drug-induced plasticity are unclear. Because Narp is an immediate early gene product that is secreted at synaptic sites and binds to alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors, it has been implicated in mediating enduring forms of synaptic plasticity. In previous studies, the authors found that Narp is selectively induced by morphine withdrawal in the extended amygdala, a group of limbic nuclei that mediate aversive behavioral responses. Accordingly, in this study, the authors evaluate whether long-term aversive effects of morphine withdrawal are altered in Narp knockout (KO) mice. The authors found that acute physical signs of morphine withdrawal are unaffected by Narp deletion. However, Narp KO mice acquire and sustain more aversive responses to the environment conditioned with morphine withdrawal than do wild type (WT) controls. Paradoxically, Narp KO mice undergo accelerated extinction of this heightened aversive response. Taken together, these studies suggest that Narp modulates both acquisition and extinction of aversive responses to morphine withdrawal and, therefore, may regulate plasticity processes underlying drug addiction. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Distinguished Scientific Award for the Application of Psychology.

Discusses contributions in behavioral pharmacology and drug abuse research made by Charles R. Schuster, the 1992 recipient of the Distinguished Scientific Award for the Application of Psychology awarded by the American Psychological Association. Schuster applied concepts and methods from the experimental analysis of behavior to the study of drugs of abuse and was a pioneer in the use of human Ss for behavioral pharmacology research. He has researched learning in adaption to repeated drug use and developed and used procedures for studying drug-taking behavior under controlled laboratory conditions. Schuster was a recent director of the National Institute on Drug Abuse, where he fostered use of scientific research to the improvement of drug abuse treatment and prevention. His biography is given. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Progress and needs in the experimental analysis of drug and alcohol dependence.

Examines the literature on drug dependence from a behavioral viewpoint. Dependence on drugs and alcohol results from an interaction between the individual and the substance within precipitating environmental conditions. Animals and humans self-administer the same drugs, suggesting the biological normality of chemical dependency and the value of laboratory research on the generation and alleviation of such dependencies. Functional or behavioral toxicity can be a serious social problem, and research is needed on why many individuals do not become addicted to drugs and alcohol to which they are exposed, and how social processes can be used to increase an individual's resistance to substance abuse. The cost effectiveness of drug research and treatment is also discussed. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Coming out of the fog: Professional practice issues in the addictions in the decade of the 1990s.

Prerequisites for progress to be made toward the appropriate assignment of clients to the most cost-effective addiction treatments include (1) more communication between researchers and clinicians with findings from basic research being integrated into clinical practice, (2) increased focus on the assessment process, (3) flexibility in treatments that are available, (4) cooperation between members of the traditional substance abuse and mental health fields, (5) a clear definition of who is an addiction specialist, and (6) integration within the addiction treatment community. (0 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Differential effects of GABA(A) and GABA(B) agonists on sensitization to the locomotor stimulant effects of ethanol in DBA/2 J mice

Contemporary theories of drug abuse suggest that behavioral sensitization plays an important role in addiction. However, few studies have examined the mechanisms underlying behavioral sensitization to ethanol. The present study examined the ability of THIP (2, 4, or 8 mg/kg) and baclofen (5.0, 6.25, or 7.5 mg/kg), GABA(A) and GABA(B) agonists, respectively, to prevent development of sensitization to the locomotor stimulant effects of ethanol (2 g/kg) in DBA/2 J mice. Ethanol was administered immediately before four 5-min activity trials conducted at 48-h intervals. Administration of ethanol on each of the four trials resulted in behavioral sensitization in control groups. While having few effects on activity when given alone, both GABA agonists completely blocked the acute stimulant response to ethanol on the first trial. Administration of THIP prior to ethanol on each trial failed to prevent development of sensitization. In contrast, all doses of baclofen blocked sensitization. Assessment of blood ethanol levels 15, 50 and 100 min after administration of ethanol indicated that baclofen did not change the pharmacokinetics of ethanol. These results indicate an important role for GABA(B) receptors, but not GABA(A) receptors, in development of sensitization to the locomotor stimulant effects of ethanol.