Chronic atomoxetine treatment during adolescence decreases impulsive choice, but not impulsive action, in adult rats and alters markers of synaptic plasticity in the orbitofrontal cortex

Sun, HaoSheng; Cocker, Paul J.; Zeeb, Fiona D.; Winstanley, Catharine A.

doi:10.1007/s00213-011-2419-9

Cited by 78 publications

(58 citation statements)

References 118 publications

(134 reference statements)

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“…Impulsive choice (cognitive impulsivity) involves various risk and decision-making behaviours, which are shown to be mediated by dissociable brain substrates and neurotransmitter system [68,69]. In accordance with our study, experiments on animals [42,43] and humans [44][45][46] have indicated that BDNF levels are affected by conditions that are described by disruptions in the control of impulses.…”

Section: Discussionsupporting

confidence: 68%

“…In addition, higher BDNF production has also been associated with various forms of impulse control disorders, such as severe gambling disorder [37], attention deficit hyperactivity disorder [38], personality disorders with high impulsiveness [39,40], and novel psychoactive substance use [41]. Experiments on animals [42,43] as well on humans [44][45][46] have indicated that BDNF levels are affected by conditions that are described by disruptions in the control of impulses. However, little is known to date about neurobiological factors associated with more specific manifestation of impulsivity, for example, risk-taking or factors that may predispose drug users to increased risk-taking behaviours.…”

Section: Introductionmentioning

confidence: 99%

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Increased Risk-Taking Behaviour and Brain-Derived Neurotrophic Factor Val66Met Polymorphism Correlates to Decreased Serum Brain-Derived Neurotrophic Factor Level in Heroin Users

Roviš¹,

Černelič-Bizjak²,

Vasiljev³

et al. 2018

Eur Addict Res

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Background: This study has examined the relationships and interactions between serum brain-derived neurotrophic factor (BDNF) levels, BDNF Val66Met polymorphism and self-reported risk-taking behaviour in individuals with a history of heroin use undergoing outpatient treatment in comparison to healthy individuals. Methods: We enrolled 167 heroin users and 86 healthy subjects and examined serum BDNF levels, Val66Met polymorphism, and personal characteristics using Connor Davidson Resilience Scale, Risk-taking (RT) propensity questionnaire, and Personality Assessment Inventory. Results: Heroin users had significantly higher serum BDNF levels than controls. In addition, serum BDNF levels were significantly higher in Val/Val carriers than in Met/Val or Met/Met in all recruited subjects. Furthermore, a stepwise multiple regression analysis of serum BDNF levels as a dependent variable with related factors showed that in heroin users, Alcohol Use Disorder Identification Test score, anxiety and RT score were found as independent contributors to serum BDNF levels. When performing gene-environment interaction it was additionally found that heroin users with self-reported high risk-taking behaviour had significantly lower levels of serum BDNF among heroin users with the Met allele. Conclusions: These results indicate that genetic variant Met66 decreased the serum BDNF levels in combination with self-reported risk-taking propensity among heroin users. If results of future work confirm the influence of this combined effect between neurotrophic genotype and risk-taking behaviour, 66Met carriers might require higher levels of intervention to overcome their drug use pattern and risky behaviour.

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Section: Discussionsupporting

confidence: 68%

Section: Introductionmentioning

confidence: 99%

Increased Risk-Taking Behaviour and Brain-Derived Neurotrophic Factor Val66Met Polymorphism Correlates to Decreased Serum Brain-Derived Neurotrophic Factor Level in Heroin Users

Roviš¹,

Černelič-Bizjak²,

Vasiljev³

et al. 2018

Eur Addict Res

View full text Add to dashboard Cite

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“…In humans, children with ADHD who are considered to be more impulsive showed either an increase in impulsive action or impulsive choice, but behavior on the two types of tasks was not correlated (Sonuga-Barke, 2002). In addition, a recent study found that adolescent atomoxetine treatment decreases impulsive choice without affecting impulsive action in adulthood (Sun et al, 2012). Therefore, exposure to high levels of stress hormones during adolescence may manifest as differential risk for certain psychiatric diseases.…”

Section: Discussionmentioning

confidence: 99%

Chronic Corticosterone Exposure during Adolescence Reduces Impulsive Action but Increases Impulsive Choice and Sensitivity to Yohimbine in Male Sprague-Dawley Rats

Torregrossa

Xie

Taylor

2012

Neuropsychopharmacol

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Chronic stress during adolescence is associated with an increased risk for alcoholism and addictive disorders. Addiction is also associated with increased impulsivity, and stress during adolescence could alter cortical circuits responsible for response inhibition. Therefore, the present study determined the effect of chronic exposure to the stress hormone corticosterone (CORT) during adolescence on tests of impulsivity in adulthood and examined possible biochemical mechanisms. Male Sprague-Dawley rats were exposed to CORT by their drinking water during adolescence (post-natal day 30-50). The rats were then tested in adulthood to assess behavior on the 5-choice serial reaction time task (5CSRTT), stop-signal reaction time task (SSRTT), and the delay-discounting task, which differentially assess attention, impulsive action, and impulsive choice. Yohimbine-induced impulsivity on the 5CSRTT and biochemical analysis of the lateral orbital frontal cortex (lOFC) was also assessed owing to the ability of yohimbine to activate the hypothalamic-pituitary-adrenal axis and influence impulsivity. Adolescent CORT-treated rats were found to behave largely like controls on the 5CSRTT, but did show reduced premature responses when the intertrial interval was increased. Nevertheless, the CORT-treated rats tended to have more yohimbineinduced impulsive responses at low doses on this task, which was not found to be due to increased pCREB in the lOFC, but could be related to a higher expression/activity of the AMPA receptor subunit GluR1. Adolescent CORT-treated rats performed more accurately on the SSRTT, but showed greater impulsivity on the delay-discounting task, as indicated by steeper discounting functions. Therefore, adolescent CORT exposure reduced impulsive action but increased impulsive choice, indicating that chronic stress hormone exposure in adolescence can have long-term consequences on behavior.

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“…Once stable baseline behavior had been established, drugs were administered in the following order: amphetamine (0, 0.3, 0.6, 1.0 mg/kg; Sun et al, 2012), ethanol (0, 0.3, 0.6, 1.0 g/kg; Bizarro et al, 2003), and caffeine (0, 5, 10, 20 mg/kg; Bizarro et al, 2004). d-amphetamine sulfate was purchased under a Health Canada exemption from Sigma-Aldrich, UK (Dorset, England), caffeine was purchased from SigmaAldrich Canada (Oakville, ON, Canada), and ethyl alcohol was purchased from Fisher Scientific (Edmonton, AB, Canada).…”

Section: Pharmacological Challengesmentioning

confidence: 99%

Sensitivity to Cognitive Effort Mediates Psychostimulant Effects on a Novel Rodent Cost/Benefit Decision-Making Task

Cocker

Hosking

Benoit

et al. 2012

Neuropsychopharmacol

107

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Amotivational states and insufficient recruitment of mental effort have been observed in a variety of clinical populations, including depression, traumatic brain injury, post-traumatic stress disorder, and attention deficit hyperactivity disorder. Previous rodent models of effort-based decision making have utilized physical costs whereas human studies of effort are primarily cognitive in nature, and it is unclear whether the two types of effortful decision making are underpinned by the same neurobiological processes. We therefore designed a novel rat cognitive effort task (rCET) based on the 5-choice serial reaction time task, a well-validated measure of attention and impulsivity. Within each trial of the rCET, rats are given the choice between an easy or hard visuospatial discrimination, and successful hard trials are rewarded with double the number of sugar pellets. Similar to previous human studies, stable individual variation in choice behavior was observed, with 'workers' choosing hard trials significantly more than their 'slacker' counterparts. Whereas workers 'slacked off' in response to administration of amphetamine and caffeine, slackers 'worked harder' under amphetamine, but not caffeine. Conversely, these stimulants increased motor impulsivity in all animals. Ethanol did not affect animals' choice but invigorated behavior. In sum, we have shown for the first time that rats are differentially sensitive to cognitive effort when making decisions, independent of other processes such as impulsivity, and these baseline differences can influence the cognitive response to psychostimulants. Such findings could inform our understanding of impairments in effort-based decision making and contribute to treatment development.

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Chronic atomoxetine treatment during adolescence decreases impulsive choice, but not impulsive action, in adult rats and alters markers of synaptic plasticity in the orbitofrontal cortex

Abstract: These data suggest that repeated administration of atomoxetine in adolescence can lead to stable decreases in impulsive choice during adulthood, potentially via modulating development of the orbitofrontal cortex.

Cited by 78 publications

References 118 publications

Increased Risk-Taking Behaviour and Brain-Derived Neurotrophic Factor Val66Met Polymorphism Correlates to Decreased Serum Brain-Derived Neurotrophic Factor Level in Heroin Users

Increased Risk-Taking Behaviour and Brain-Derived Neurotrophic Factor Val66Met Polymorphism Correlates to Decreased Serum Brain-Derived Neurotrophic Factor Level in Heroin Users

Chronic Corticosterone Exposure during Adolescence Reduces Impulsive Action but Increases Impulsive Choice and Sensitivity to Yohimbine in Male Sprague-Dawley Rats

Sensitivity to Cognitive Effort Mediates Psychostimulant Effects on a Novel Rodent Cost/Benefit Decision-Making Task

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