Modulation of high impulsivity and attentional performance in rats by selective direct and indirect dopaminergic and noradrenergic receptor agonists

Fernando, Anushka B. P.; Economidou, Daina; Theobald, David E.; Zou, Mu‐Fa; Newman, Amy Hauck; Spoelder, Marcia; Caprioli, Daniele; Moreno, Margarita; Hipólito, Lucía; Aspinall, Albert T.; Robbins, Trevor W.; Dalley, Jeffrey W.

doi:10.1007/s00213-011-2408-z

Cited by 123 publications

(146 citation statements)

References 60 publications

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“…The observed effects of atomoxetine are in general agreement with results obtained in Wistar rats during choice behavior in T-maze [8] and in Lister hooded rats in the five-choice serial reaction time task [31]. The results also parallel improvement in visuo-spatial performance in children with ADHD after subchronic atmoxetine [32].…”

Section: Discussionsupporting

confidence: 86%

Enrichment Discrimination Behavior in Spontaneously Hypertensive Rats

Salimov¹,

Ковалев²

2012

JBBS

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Objectives: 1) To reveal, among spontaneously hypertensive rats, subpopulations that diverge in attention to objects enriching an empty cross-maze; 2) To evaluate effect of clinically efficient drug for treatment of attention deficiency atomoxetine on the attention to environmental cues in attentionally-low rats. Method: A novel paradigm that provides measure of attention towards enriching objects independent of general locomotor activity and spatial orientation is employed. The apparatus consists of 4-arm radial maze, two arms of which contain objects (enriched compartments). Animals exploring the objects typically stay longer in enriched parts of maze than in empty arms and have a higher score of enrichment discrimination ratio. Results: Frequency distribution of the enrichment discrimination ratio had clear bimodal shape that differed significantly from normal distribution suggesting the existence of subpopulations of attentionally-low and -high individuals. The attentionally-low phenotype did not show inferiority in spatial orientation as compared with attentionally-high phenotype. The phenotypes did not differ from each other in measures of locomotor activity and blood pressure. Atomoxetine (3 mg/kg, orally, once daily for 4 days) enhanced enrichment discrimination in animals of attentionally-low phenotype. Single administration of the drug was ineffective. Conclusion: Population of spontaneously hypertensive rat includes two phenotypes of attentionally-low and -high individuals. Subchronic atomoxetine ameliorates attention to environmental cues in attentionally-low rats. The enrichment discrimination test could be useful in studies of neurobiology of attention deficit condition and for screening of novel drug candidates.

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Section: Discussionsupporting

confidence: 86%

Enrichment Discrimination Behavior in Spontaneously Hypertensive Rats

Salimov¹,

Ковалев²

2012

JBBS

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“…Amelioration of high impulsivity has been reported for rats chronically self-administering cocaine (Dalley et al 2007) and for experimenter-administered methylphenidate, the D2/3 receptor agonist quinpirole or atomoxetine (Fernando et al 2012). Methylphenidate also caused an upregulation of D2/3 receptors in high-impulsive rats but the opposite neural (and behavioral) effects in controls (Caprioli et al 2014).…”

Section: Addiction Endophenotypes In Experimental Animalsmentioning

confidence: 95%

Drug Addiction: Updating Actions to Habits to Compulsions Ten Years On

Everitt

Robbins

2016

Annu. Rev. Psychol.

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949

773

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A decade ago, we hypothesized that drug addiction can be viewed as a transition from voluntary, recreational drug use to compulsive drug-seeking habits, neurally underpinned by a transition from prefrontal cortical to striatal control over drug seeking and taking as well as a progression from the ventral to the dorsal striatum. Here, in the light of burgeoning, supportive evidence, we reconsider and elaborate this hypothesis, in particular the refinements in our understanding of ventral and dorsal striatal mechanisms underlying goal-directed and habitual drug seeking, the influence of drug-associated Pavlovian-conditioned stimuli on drug seeking and relapse, and evidence for impairments in top-down prefrontal cortical inhibitory control over this behavior. We further review animal and human studies that have begun to define etiological factors and individual differences in the propensity to become addicted to drugs, leading to the description of addiction endophenotypes, especially for cocaine addiction. We consider the prospect of novel treatments for addiction that promote abstinence from and relapse to drug use.

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“…Consistent with these results, the a 2 -adrenergic receptor agonist guanfacine [N-(diaminomethylidene)-2-(2,6-dichlorophenyl) acetamide] suppressed, while the a 2 -adrenergic receptor antagonist yohimbine (methyl (1S,15R,18S,19R,20S)-18-hydroxy-1,3,11,12,14,15,16,17,18,19,20,21-dodecahydroyohimban-19-carboxylate) increased, 5-CSRTT premature responses in rats (Sun et al, 2010;Fernando et al, 2012;Pillidge et al, 2014). Thus, while more work remains to clarify the role of specific a 1 -and a 2 -adrenergic subtypes on 5-CSRTT and DRL 72-second behavior, converging pharmacological evidence for NET inhibitors and b 2 -, a 1 -, and a 2 -adrenergic receptor agonists supports the hypothesis that motoric impulsivity is an important aspect for both behavioral paradigms.…”

Section: Rethinking An Empirical Antidepressant Screenmentioning

confidence: 99%

The Utility of Impulsive Bias and Altered Decision Making as Predictors of Drug Efficacy and Target Selection: Rethinking Behavioral Screening for Antidepressant Drugs

Marek

Day

Hudzik

2015

Journal of Pharmacology and Experimental Therapeutics

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Cognitive dysfunction may be a core feature of major depressive disorder, including affective processing bias, abnormal response to negative feedback, changes in decision making, and increased impulsivity. Accordingly, a translational medicine paradigm predicts clinical action of novel antidepressants by examining drug-induced changes in affective processing bias. With some exceptions, these concepts have not been systematically applied to preclinical models to test new chemical entities. The purpose of this review is to examine whether an empirically derived behavioral screen for antidepressant drugs may screen for compounds, at least in part, by modulating an impulsive biasing of responding and altered decision making. The differential-reinforcement-of-low-rate (DRL) 72-second schedule is an operant schedule with a documented fidelity for discriminating antidepressant drugs from nonantidepressant drugs. However, a theoretical basis for this empirical relationship has been lacking. Therefore, this review will discuss whether response bias toward impulsive behavior may be a critical screening characteristic of DRL behavior requiring long interresponse times to obtain rewards. This review will compare and contrast DRL behavior with the five-choice serial reaction time task, a test specifically designed for assessing motoric impulsivity, with respect to psychopharmacological testing and the neural basis of distributed macrocircuits underlying these tasks. This comparison suggests that the existing empirical basis for the DRL 72-second schedule as a pharmacological screen for antidepressant drugs is complemented by a novel hypothesis that altering impulsive response bias for rodents trained on this operant schedule is a previously unrecognized theoretical cornerstone for this screening paradigm.

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Modulation of high impulsivity and attentional performance in rats by selective direct and indirect dopaminergic and noradrenergic receptor agonists

Cited by 123 publications

References 60 publications

Enrichment Discrimination Behavior in Spontaneously Hypertensive Rats

Enrichment Discrimination Behavior in Spontaneously Hypertensive Rats

Drug Addiction: Updating Actions to Habits to Compulsions Ten Years On

The Utility of Impulsive Bias and Altered Decision Making as Predictors of Drug Efficacy and Target Selection: Rethinking Behavioral Screening for Antidepressant Drugs

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