Harriet de Wit

..In parallel, additional investigation of initial responses in animal models as predictors of drug use will shed light on the underlying mechanisms...

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..The findings lay the groundwork for studying the cognitive and neurobiological substrates of impulsivity, and for future studies on the role of impulsive behavior as both facilitator and a result of drug use...

..In general, the results with these doses indicate that the abuse potential of pagoclone is similar to that of diazepam, although its profile as a partial agonist suggests that differences between the drugs may emerge at higher doses...

..The significant relationship between DRD2 genotype and both behavioral inhibition and impulsivity suggests a possible common genetic influence on behavioral and self-report measures of impulsivity...

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..These findings support the idea that the drug has psychoactive effects even in the absence of withdrawal...

..Despite their apparent importance in recreational and potential psychotherapeutic use of MDMA, the defining characteristics and neurobiological mechanisms of these interpersonal effects are poorly understood...

..One way that drugs may affect social behavior is by altering social processing, for example by decreasing perceptions of negative emotion in others...

..Relapse to smoking is often precipitated by stress, yet little is known about the effects of nicotine withdrawal on responses to acute stress, or whether nicotine replacement reverses withdrawal-induced changes in stress response...

..It is important to understand how smoking affects physiological and psychological outcomes after stress and how these may interact to motivate smoking...

..We previously found that the intronic norepinephrine transporter gene (SLC6A2) polymorphism rs36017 modulates feelings of elation after administration of 20 mg D-amphetamine in healthy volunteers...

..Post-error slowing has long been considered a sign of healthy error detection and an important component of cognitive function. However, the neuropharmacological processes underlying post-error slowing are poorly understood...

..This observation extends prior findings implicating a cortico-limbic, emotion-related central mechanism underlying cannabinoid function...

..In this study, we investigated whether different phases of response to an acute stress alter the subjective effects of intravenous alcohol, by administering the drug at 2 different times after the stress...

..We discuss our findings in the context of sex differences in the prevalence of stress-linked disorders...

..The dissociations between the four measures of impulsivity suggest that impulsivity is an assemblage of distinct components rather than a unitary process...

..These findings suggest a pleiotropic effect of this polymorphic locus on both ADHD and sensitivity to the subjective effects of amphetamine...

..It is likely that other ADORA2A and DRD2 polymorphisms also contribute to responses to caffeine...

..It has been postulated that either lower or greater acute responses to alcohol, or both, depending on the limb of the breath alcohol concentration curve, contribute to propensity for alcohol misuse...

..Similarly, stress may also alter the acute subjective effects of drugs or the tendency to seek and consume drugs in humans...

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..These findings help elucidate neurochemical substrates of choice, with implications for neuropsychiatric diseases characterized by dopaminergic dysfunction and motivational deficits...

..Here, we extend these observations by examining two measures of cognitive function, lapses in attention and visuo-spatial-motor speed of processing, in both the drug-free state and after administration of d-amphetamine...

..The findings extend existing data on sex differences in the effects of either nicotine or cigarette smoking on alcohol consumption, and support the idea that the pharmacological effects of nicotine may differ in men and women...

..These results support our previous work, and show that THC reduces perception of facial threat. Nevertheless, THC does not appear to positively bias evaluation of emotional stimuli in general...

..In this study, we examined the effects of an acute dose of VAR upon subjective, physiological, and objective responses to low and moderate doses of alcohol in healthy social drinkers...

..e., euphoria). However, recent findings suggest drugs may also alter emotional reactivity to external stimuli, and that this may occur independently of direct effects on mood...

..Thus, the findings suggest that sleep loss may increase the likelihood of smoking during abstinence not through inhibitory or attentional mechanisms but because of the potential of nicotine to reduce subjective sleepiness...

..Thus, progesterone dampened some of the psychological effects of stress but produced inconsistent effects on physiological stress responses...

..The sedative-like effects observed in this study may reflect presynaptic actions of the drug. Higher doses with postsynaptic actions may be needed to produce either behavioral or subjective stimulant-like effects...

..These results suggest that low doses of diazepam, including doses that are used therapeutically, do not increase impulsive behavior. Whether higher doses would increase impulsivity remains to be determined...

..001), which corresponded to a leftward shift in the dose-response curve. These findings demonstrate the successful translation of pharmacogenetic results from mice to humans...

..These findings indicate that consumption of a caffeine-containing food supplement improves subjective state and cognitive performance in fatigued individuals that is likely a result of its caffeine content...

..CONCLUSION: These results provide only limited support for the idea that nicotinic acetylcholine receptors are involved in the rewarding effects of alcohol...

..Here we examined the effects of an acute social stressor (performing a mental arithmetic task in front of an audience) on consumption of ethanol or placebo beverages in healthy social drinkers...

..Further, we investigated the relationship between conditioned place preference and the mood-altering effects of the drug...

..Further research may help determine whether alteration in cortisol response to alcohol is a biological marker of the propensity to abuse alcohol...

..The findings suggest that the TSST may be conducted with multiple participants without significantly affecting subjective and cortisol responses to the task...

..Our approach provides a case study for analysis of high-dimensional intermediate pharmacogenomic phenotypes, which may be more tractable than clinical diagnoses...

..Moreover, humans synthesize 5beta-reduced GABAergic steroids, and levels of these steroids may be altered in plasma or brain...

..CONCLUSIONS: These findings suggest that nicotinic cholinergic receptors are involved in mediating some of the stimulant-like effects of alcohol...

..The findings of this study contribute to a growing literature indicating that nicotine differentially affects specific subtypes of cognitive performance in healthy nonsmokers...

..If confirmed, these results could lead to a better understanding of personality traits and inter-individual susceptibility developing psychiatric disorders such as major depression...

..These results suggest that acute doses of amphetamine decrease several forms of impulsive behavior. These findings extend and confirm previous findings in humans and laboratory animals...

..These results are discussed in the context of other recent findings suggesting that different behavioral indices of impulsivity are dissociable and governed by separate underlying mechanisms...

..Recommendations for the measurement of "Voluntary Talkativeness" are made...

..Thus, higher levels of estrogen and lower levels of progesterone are associated with greater subjective stimulation after AMPH in women, and these hormonal influences contribute to sex differences in amphetamine responding...

..This study provides a starting point for exploring contributions of the adenosine system to motivation in humans...

..However, they have yet to be characterized in controlled studies. Here, we investigate effects of MDMA on an important social cognitive capacity, the identification of emotional expression in others, and on socially relevant mood states...

..Lack of effect on impulsivity stands in contrast to other studies in which other psychoactive drugs including ethanol, delta-9-tetrahydrocannabinol, and amphetamine altered behavior on one or more behavioral measures of impulsivity...

..quot; It is unknown whether cue-induced craving increases, decreases, or remains constant with abstinence in humans. We investigated effects of abstinence on cue-induced craving in cigarette smokers...

..Several psychoactive drugs are known to influence episodic memory. However, these drugs' effects on false memory, or the tendency to incorrectly remember nonstudied information, remain poorly understood...

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..They also highlight a specific neurocognitive mechanism that may contribute to increased risk for addiction...

..However, other factors, such as early-age heavy drinking, are also risk factors for sustained or progressive heavy consumption. Little is currently known about the mechanisms underlying binge or heavy drinking...

..NAC lesions may disrupt the ability of the animals to predict the timing of delayed rewards when the delay to reward is changed frequently...

..Despite its widespread use, relatively little is understood regarding how genetics affects consumption, acute response, or the long-term effects of caffeine...

..The results suggest continued examination of naltrexone as an adjunct in smoking cessation, particularly in female smokers, who have historically shown worse outcomes with traditional treatment methods...

..Data from an in vitro study suggests that combined, sub-threshold doses of these drugs may interact to produce synergistic effects. Very low doses of the two drugs in combination have not been tested in humans...

..In this study, we investigated the effects of acute psychosocial stress on cigarette craving, the subjective effects of smoking, and smoking behavior in daily smokers...

..The finding that acute administration of exogenous estradiol did not alter mood suggests that more chronic exposure to estradiol is needed to produce mood-enhancing effects...

..This line of research may also improve our understanding of the neurochemical mechanisms underlying the drug dependence process...

..With other drugs, the evidence to date suggests that ovarian hormones have modest, if any, effects on responses to abused drugs. We discuss methodological issues relating to inclusion of women with regular menstrual cycles...

..The stressor was a modified version of the Trier Social Stress Test, an arithmetic task that increases cortisol levels...

..Parallel studies in rats and humans are important to validate the large body of neurobiological research with non-human species to humans...

..These results suggest that BDNF is related to the subjective and physical response to low doses of AMPH...

..The study shows that an adenosine receptor gene polymorphism that has been associated with Panic Disorder is also associated with anxiogenic responses to an acute dose of caffeine...

..These results suggest that both AMPH and smoking abstinence can increase cigarette craving, but they do not appear to specifically affect responses to conditioned smoking-related cues...

..The current findings have important implications for understanding the genetic determinants of variability in stimulant response and risk of abuse...

..These results suggest that bupropion improves attention without affecting impulsive behavior in healthy adults. Improvements in attention may contribute to the effectiveness of bupropion as a pharmacotherapy for smoking...

..CONCLUSIONS: These results suggested that the direct effects of MOR may contribute to the high level of impulsive behavior seen among opiate users...

..Implications for the vulnerability to psychostimulant addiction in healthy nonaddicts are discussed...

..e., 6% each of the present sample), and it may transiently increase, rather than decrease, smoking during early phases of treatment in continuing smokers...

..There was evidence of discriminant validity between the AgPEM, NEM, and CON dimensions and behavioral responses to amphetamine. Implications for treatment and addiction are discussed. (c) 2008 APA, all rights reserved...

..Because the effects of amphetamine are mediated in part by the norepinephrine transporter (SLC6A2), we examined interindividual differences in mood response to amphetamine in relation to SLC6A2 gene polymorphisms...

..The separate and combined analyses of the gene-linked polymorphic region (5-HTTLPR) and the Intron 2 VNTR suggest that these two HTT polymorphisms may contribute to acute subjective responses to d-amphetamine with a small effect...

..The results indicate that sleep deprivation does not specifically increase impulsive behaviors but may differentially affect risk taking in men and women...

..This is consistent with recent observations indicating a role for adenosine A(2A) receptor gene polymorphisms in anxiety...

..b>Harriet de Wit summarized and discussed the research presented at the symposium and provided her perspective on future ..

..Finally, there appears to be a good correspondence between the events that induce reinstatement in laboratory animals and those that provoke relapse in humans...

..The goal of the study was to better understand variations in responses to psychostimulants in healthy volunteers...

..Dr. David Goldman provides concluding remarks...

..The EDT was more sensitive to the acute effects of alcohol than previously used discounting tasks. Procedural differences between the EDT and question-based measures are discussed in the context of these divergent findings...

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..abstract_text> ..

..Together, the studies will extend our understanding of the source of individual differences in responses to abused drugs, and they will further our knowledge of the interactions of drugs and hormones in the brain. ..

..Clinically, the projects may lead to novel strategies for preventing and treating substance abuse. ..

..The project is the result of a unique collaboration among basic and clinical scientists at the University of Chicago and the NIDA Intramural Research Program. ..

..The results of these studies will improve our understanding of mechanisms by which stress increases drug use, and could lead to improved methods for preventing and treating stress-related drug use. ..

..Clinically, the projects may lead to novel strategies for preventing and treating substance abuse. ..

..The experiments are designed to explore variables that affect the reinforcing effects of drugs, and the results may elucidate some of the determinants of drug abuse...