Contrasting Roles for Dopamine D1 and D2 Receptor Subtypes in the Dorsomedial Striatum but Not the Nucleus Accumbens Core during Behavioral Inhibition in the Stop-Signal Task in Rats

Eagle, Dawn M.; Wong, Jacky C K; Allan, Michelle E; Mar, Adam C.; Theobald, David E.; Robbins, Trevor W.

doi:10.1523/jneurosci.6182-10.2011

Cited by 138 publications

(132 citation statements)

References 52 publications

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“…By contrast, the PR trials of our loss-chasing task require rats to monitor a single location for visual targets and execute simple nose-poke responses to gain rewards. On this view, our findings can be reconciled with earlier reports by noting the greater involvement of D 1 receptor activity in selective attentional aspects of the 5-CSRTT (including speedy and accurate responding), and involvement of D 2 receptors in the control over single prepared responses in our loss-chasing task (Eagle et al, 2011). More specifically, our finding that 8-OH-DPAT and eticlopride reduced the proportion of chase responses (and the number of consecutive chases per episode) and premature responses (on PR trials) point to links between aspects of gambling behavior and inhibitory control, exemplified by reports in human subjects that the control of betting behavior can be facilitated by successful inhibition of unrelated motor acts (Verbruggen et al, 2012).…”

Section: Discussionsupporting

confidence: 85%

Systemic Administration of 8-OH-DPAT and Eticlopride, but not SCH23390, Alters Loss-Chasing Behavior in the Rat

Rogers

Wong

McKinnon

et al. 2013

Neuropsychopharmacol

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Gambling to recover losses is a common gaming behavior. In a clinical context, however, this phenomenon mediates the relationship between diminished control over gambling and the adverse socioeconomic consequences of gambling problems. Modeling loss-chasing through analogous behaviors in rats could facilitate its pharmacological investigation as a potential therapeutic target. Here, rats were trained to make operant responses that produced both food rewards, and unpredictably, imminent time-out periods in which rewards would be unavailable. At these decision points, rats were offered choices between waiting for these time-out periods to elapse before resuming responding for rewards ('quit' responses), or selecting risky options with a 0.5 probability of avoiding the time-outs altogether and a 0.5 probability of time-out periods twice as long as signaled originally ('chase' responses). Chasing behavior, and the latencies to chase or quit, during sequences of unfavorable outcomes were tested following systemic administration of the 5-HT 1A receptor agonist, 8-OH-DPAT, the D 2 receptor antagonist, eticlopride, and the D 1 receptor antagonist, SCH23390. 8-OH-DPAT and eticlopride significantly reduced the proportion of chase responses, and the mean number of consecutive chase responses, in a dose-dependent manner. 8-OH-DPAT also increased latencies to chase. Increasing doses of eticlopride first speeded, then slowed, latencies to quit while SCH23390 had no significant effects on any measure. Research is needed to identify the precise cognitive mechanisms mediating these kinds of risky choices in rats. However, our data provide the first experimental demonstration that 5-HT 1A and D 2 , but not D 1 , receptor activity influence a behavioral analog of loss-chasing in rats.

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Section: Discussionsupporting

confidence: 85%

Systemic Administration of 8-OH-DPAT and Eticlopride, but not SCH23390, Alters Loss-Chasing Behavior in the Rat

Rogers

Wong

McKinnon

et al. 2013

Neuropsychopharmacol

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“…For example, whereas yohimbine-induced impulsivity involves activation of specific signaling cascades in the lOFC (Sun et al, 2010), lesions of the infralimbic region of PFC, not lOFC, have been reported to increase impulsive responding in the face of increasing ITIs on the 5CSRTT (Chudasama et al, 2003). Similarly, behavioral inhibition on the SSRTT may be more dependent on dorsal medial PFC and dorsal striatal activity (Bari et al, 2011;Eagle and Robbins, 2003a;Eagle et al, 2011), whereas choice behavior on the delay-discounting task may be more dependent on a circuit involving the lOFC and ventral striatum (Bezzina et al, 2008;Bezzina et al, 2007;Mobini et al, 2002). Whatever the mechanism, an increase in the likelihood of making impulsive decisions, particularly for immediate 'gratification', could certainly put individuals at a higher risk for developing addictive disorders.…”

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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“…Beyond these divergent clinical results, animal studies are also controversial [40]. Nevertheless, Eagle and colleagues showed recently that DA can have opposing functions on inhibitory systems depending on the receptors under scrutiny [41]. If DA is involved specifically in proactive inhibition, we hypothesize that PD patients under dopaminergic treatment should improve movement initiation latency even more when proactive inhibition is required.…”

Section: A Dopaminergic Origin Of Akinesia?mentioning

confidence: 99%

Deep Brain Stimulation of the Subthalamic Nucleus, but not Dopaminergic Medication, Improves Proactive Inhibitory Control of Movement Initiation in Parkinson's Disease

et al. 2013

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Slowness in movement initiation is a cardinal feature of Parkinson's disease (PD) that is still poorly understood and unsuccessfully alleviated by standard therapies. Here, we raise this major clinical issue within the framework of a novel theoretical model that allows a better understanding of the basic mechanisms involved in movement initiation. This model assumes that movement triggering is inhibited by default to prevent automatic responses to unpredictable events. We investigated to which extent the top-down control necessary to release this locking state before initiating actions is impaired in PD and restored by standard therapies. We used a cue-target reaction time task to test both the ability to initiate fast responses to targets and the ability to refrain from reacting to cues. Fourteen patients with dopaminergic (DA) medication and 11 with subthalamic nucleus (STN) stimulation were tested on and off treatment, and compared with 14 healthy controls. We found evidence that patients withdrawn from treatment have trouble voluntarily releasing proactive inhibitory control; while DA medication broadly reduces movement initiation latency, it does not reinstate a normal pattern of movement initiation; and stimulation of the STN specifically re-establishes the efficiency of the top-down control of proactive inhibition. These results suggest that movement initiation disorders that resist DA medication are due to executive, not motor, dysfunctions. This conclusion is discussed with regard to the role the STN may play as an interface between non-DA executive and DA motor systems in cortico-basal ganglia loops.

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Contrasting Roles for Dopamine D1 and D2 Receptor Subtypes in the Dorsomedial Striatum but Not the Nucleus Accumbens Core during Behavioral Inhibition in the Stop-Signal Task in Rats

Cited by 138 publications

References 52 publications

Systemic Administration of 8-OH-DPAT and Eticlopride, but not SCH23390, Alters Loss-Chasing Behavior in the Rat

Systemic Administration of 8-OH-DPAT and Eticlopride, but not SCH23390, Alters Loss-Chasing Behavior in the Rat

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

Deep Brain Stimulation of the Subthalamic Nucleus, but not Dopaminergic Medication, Improves Proactive Inhibitory Control of Movement Initiation in Parkinson's Disease

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