Effect of tryptophan depletion on impulsive behavior in men with or without a family history of alcoholism

Crean, John P.; Richards, Jerry B.; Wit, Harriet de

doi:10.1016/s0166-4328(02)00132-8

Cited by 145 publications

(135 citation statements)

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“…It is consistent with other work showing that ATD affects impulsive behavior only in certain individuals (Cherek and Lane, 1999;LeMarquand et al, 1999;Bjork et al, 2000;Marsh et al, 2002;Swann et al, 2002; but see Crean et al, 2002).…”

Section: Discussionsupporting

confidence: 92%

“…ATD did not affect SSRT, a measure of prepotent response inhibition. The negative result on SSRT in this small sample size (of 11 subjects) should be interpreted with caution and replication with a greater number of subjects should be awaited before firm conclusions can be drawn, particularly given a previous observation that ATD slowed SSRT in a group of 20 healthy men with a family history of alcoholism, while it improved SSRT in a group 20 healthy men without such a history (Crean et al, 2002). The discrepancy between the Crean et al study and our study may relate to the difference in sample size (n ¼ 20 in their study vs n ¼ 11 in our study) or the different dose: Crean et al administered 100 mg drinks, associated with an average 84% reduction of TRPÀ levels relative to baseline, while we administered 75 mg drinks, which reduced TRPÀ levels by 61% relative to baseline.…”

Section: Discussionmentioning

confidence: 85%

“…CSF concentrations of the 5-HT metabolite 5-HIAA correlate inversely with impulsive behaviors in many neuropsychiatric and personality disorders including aggressive, conduct, and attention-deficit/hyperactivity disorders (Evenden, 1999). Furthermore, recent studies with human volunteers have found that ATD increases impulsive and aggressive behavior, although these effects appear to depend on individual differences in impulsive personality traits (Cherek and Lane, 1999;LeMarquand et al, 1999;Dougherty et al, 1999;Bjork et al, 2000;Marsh et al, 2002;Crean et al, 2002). Findings from studies with clinical human populations are corroborated by an extensive number of animal studies, which suggest that impulsive choice in delaydiscounting paradigms and premature responding in choice reaction-time tasks implicate changes in the 5-HT system (Wogar et al, 1993;Harrison et al, 1997a, b;Puumala and Sirvio, 1998;Koskinen et al, 2000;Mobini et al, 2000;Dalley et al, 2002;Passetti et al, 2003;Winstanley et al, 2003;Liu et al, 2004).…”

Section: Introductionmentioning

confidence: 99%

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Tryptophan Depletion Disrupts the Motivational Guidance of Goal-Directed Behavior as a Function of Trait Impulsivity

Cools

Blackwell

Clark

et al. 2005

Neuropsychopharmacol

143

145

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Serotonin (5-HT) is well known to affect the motivational properties of stimuli predictive of rewards as well as the inhibitory control of behavior. Here, central 5-HT depletion was induced by the acute tryptophan (TRP) depletion (ATD) procedure in young healthy volunteers to examine the role of 5-HT in motivated action and prepotent response inhibition. A novel reaction-time task, tailored to individual differences in general cognitive speed, was employed to measure the guidance of behavior by motivationally relevant signals predictive of reinforcement likelihood, while the stop-signal reaction-time task was used to measure response inhibition. Following the TRP-balancing control drink, cues predictive of high-reinforcement certainty induced faster, but less accurate responses compared with cues predictive of lower reinforcement certainty. Depletion of central 5-HT modulated this coupling between motivation and action by slowing responses and increasing accuracy as a function of incentive certainty. These effects of ATD on motivated action correlated highly with individual differences in the personality trait of Nonplanning Impulsiveness (Barratt Impulsivity Scale (BIS-11)), so that strongest effects on motivated action were observed in high-impulsive individuals. By contrast, ATD left unaltered the ability to inhibit prepotent responses. Our findings may have implications for a variety of neuropsychiatric disorders including impulsive aggressive disorders and depression.

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Section: Discussionsupporting

confidence: 92%

Section: Discussionmentioning

confidence: 85%

Section: Introductionmentioning

confidence: 99%

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Tryptophan Depletion Disrupts the Motivational Guidance of Goal-Directed Behavior as a Function of Trait Impulsivity

Cools

Blackwell

Clark

et al. 2005

Neuropsychopharmacol

143

145

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“…In keeping with data obtained following tryptophan depletion in human volunteers (Crean et al, 2002), global 5-HT depletion alone had no effect on delay-discounting. This contrasts with previous studies reporting increased choice of the small, immediate reward following serotonergic lesions of the dorsal and median raphé nuclei (Mobini et al, 2000;Wogar et al, 1993).…”

Section: Discussionsupporting

confidence: 85%

“…The finding that the same neurochemical manipulation increases all these aspects of impulsivity suggests that impulsivity is a unitary construct, at least in terms of its regulation by the serotonergic system. However, data from human volunteers following tryptophan depletion, which leads to decreases in levels of 5-HT in the CNS, have consistently found increases in impulsive action, but not in impulsive choice (Crean et al, 2002;LeMarquand et al, 1999LeMarquand et al, , 1998. These data suggest that behavioral disinhibition, rather than impulsive decision-making, may be more sensitive to alterations in the serotonergic system.…”

Section: Introductionmentioning

confidence: 99%

Fractionating Impulsivity: Contrasting Effects of Central 5-HT Depletion on Different Measures of Impulsive Behavior

Winstanley

Dalley

Theobald

et al. 2004

Neuropsychopharmacol

345

280

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Reducing levels of 5-HT in the central nervous system has been associated with increases in impulsive behavior. However, the impulsivity construct describes a wide range of behaviors, including the inability to withhold a response, intolerance to delay of reward and perseveration of a nonrewarded response. Although these behaviors are generally studied using instrumental paradigms, impulsivity may also be reflected in simple Pavlovian tasks such as autoshaping and conditioned activity. This experiment aimed to characterize further the effects of central 5-HT depletion and to investigate whether different behavioral measures of impulsivity are inter-related, thus validating the construct. Rats received intracerebroventricular (ICV) infusions of vehicle (n ¼ 10) or the serotonergic neurotoxin 5,7-dihydroxytryptamine (n ¼ 12) which depleted forebrain 5-HT levels by about 90%. Lesioned animals showed significant increases in the speed and number of responses made in autoshaping, increased premature responding on a simple visual attentional task, enhanced expression of locomotor activity conditioned to food presentation, yet no change in impulsive choice was observed, as measured by a delay-discounting paradigm. Significant positive correlations were found between responses made in autoshaping and the level of conditioned activity, indicating a possible common basis for these behaviors, yet no correlations were found between other behavioral measures. These data strengthen and extend the hypothesis that 5-HT depletion increases certain types of impulsive responding. However, not all measures of impulsivity appear to be uniformly affected by 5-HT depletion, or correlate with each other, supporting the suggestion that impulsivity is not a unitary construct.

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An Overview of Measuring Impulsive Behavior in Mice

Dent

Isles

2014

CP Mouse Biology

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Impulsive behavior is a key constituent of many psychiatric illnesses, with maladaptive response control being a feature of disorders such as ADHD, schizophrenia, mania, and addiction. In order to understand the neurological underpinnings of impulsivity, a number of behavioral tasks have been developed for use with animal models. Data from studies with rats and other animals have led to the idea of the existence of dissociable components of impulsivity, which in turn informs studies of human disorders and potentially the development of specific therapies. Increasingly, mouse models are being used to investigate the known genetic contribution to psychiatric disorders in which abnormal response control leads to altered impulsive behaviors. In order to maximize the potential of these mouse models, it is important that researchers take into account the non-unitary nature of response control and impulsivity. In this article, we briefly review the tasks available to behavioral neuroscientists and how these can be used in order to tease apart the contribution of a specific genetic lesion into the discrete aspects of impulsive behavior.

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Effect of tryptophan depletion on impulsive behavior in men with or without a family history of alcoholism

Cited by 145 publications

References 50 publications

Tryptophan Depletion Disrupts the Motivational Guidance of Goal-Directed Behavior as a Function of Trait Impulsivity

Tryptophan Depletion Disrupts the Motivational Guidance of Goal-Directed Behavior as a Function of Trait Impulsivity

Fractionating Impulsivity: Contrasting Effects of Central 5-HT Depletion on Different Measures of Impulsive Behavior

An Overview of Measuring Impulsive Behavior in Mice

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