Forebrain circuitry involved in effort-related choice: Injections of the GABAA agonist muscimol into ventral pallidum alter response allocation in food-seeking behavior

Department of Psychology, University of Connecticut, Storrs, CT 06269-1020, USA.
Neuroscience (Impact Factor: 3.36). 04/2008; 152(2):321-30. DOI: 10.1016/j.neuroscience.2007.12.034
Source: PubMed


Organisms often make effort-related choices based upon assessments of motivational value and work requirements. Nucleus accumbens dopamine is a critical component of the brain circuitry regulating work output in reinforcement-seeking behavior. Rats with accumbens dopamine depletions reallocate their instrumental behavior away from food-reinforced tasks that have high response requirements, and instead they select a less-effortful type of food-seeking behavior. The ventral pallidum is a brain area that receives substantial GABAergic input from nucleus accumbens. It was hypothesized that stimulation of GABA(A) receptors in the ventral pallidum would result in behavioral effects that resemble those produced by interference with accumbens dopamine transmission. The present studies employed a concurrent choice lever pressing/chow intake procedure; with this task, interference with accumbens dopamine transmission shifts choice behavior such that lever pressing for food is decreased but chow intake is increased. In the present experiments, infusions of the GABA(A) agonist muscimol (5.0-10.0 ng) into the ventral pallidum decreased lever pressing for preferred food, but increased consumption of the less preferred chow. In contrast, ventral pallidal infusions of muscimol (10.0 ng) had no significant effect on preference for the palatable food in free-feeding choice tests. Furthermore, injections of muscimol into a control site dorsal to the ventral pallidum produced no significant effects on lever pressing and chow intake. These data indicate that stimulation of GABA receptors in ventral pallidum produces behavioral effects similar to those produced by accumbens dopamine depletions. Ventral pallidum appears to be a component of the brain circuitry regulating response allocation and effort-related choice behavior, and may act to convey information from nucleus accumbens to other parts of this circuitry. This research may have implications for understanding the brain mechanisms involved in energy-related psychiatric dysfunctions such as psychomotor retardation in depression, anergia, and apathy.

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Available from: John Salamone
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    • "There is a preferential localization of D 2 receptor/ enkephalin positive neurons in accumbens core relative to the shell (Lu et al., 1998), and a dense projection of enkephalin positive neurons that contain both D 2 and A 2A receptors and project from accumbens core to lateral ventral pallidum (Farrar et al., 2008;Ferré et al., 2008;Mingote et al., 2008;Smith et al., 2013). Considerable evidence implicates this component of the GABAergic ventral striatopallidal pathway in behavioral activation and effort-related processes (Mingote et al., 2008;Farrar et al., 2008Farrar et al., , 2010Salamone et al. 2010). Yet despite the co-localization of adenosine A 1 receptors with DA D 1 receptors on accumbens substance P-positive medium spiny neurons, the behavioral effects of D 1 antagonism are not reversed by A 1 antagonists (Collins et al., 2010;Nunes et al., 2010). "
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    ABSTRACT: Mesolimbic dopamine (DA), particularly in the nucleus accumbens, is a critical component of the brain circuitry involved in behavioral activation and effort-related processes. Although much is known about the characteristics of DA D2 receptor antagonism on effort-related choice behavior, less is known about the effects of D1 antagonism, and agonist/antagonist interactions. The highly selective D1 antagonist ecopipam was studied for its effects on effort-related choice behavior using the concurrent fixed ratio (FR) 5/chow feeding choice and T-maze barrier choice procedures. In rats tested on the FR5/chow feeding choice task, ecopipam shifted choice behavior, decreasing lever pressing for preferred high carbohydrate pellets but increasing consumption of lab chow. Also, ecopipam decreased selection of the high effort option (i.e., climbing the barrier to obtain a larger reward) in rats tested on the T-maze task, but did not disrupt arm preference or discrimination when no barrier was present. The D1 agonists SKF38393, SKF81297 and A77636 were assessed for their ability to reverse the effects of ecopipam, and in each case the D1 agonist significantly attenuated the effects of ecopipam, typically with an inverted-u shaped dose/response curve. SKF81297 also was able to reverse the effects of the catecholamine depleting agent tetrabenazine on T-maze performance. In summary, the present results implicate DA D1 receptors in the regulation of behavioral activation and effort-related functions, and demonstrate the utility of using tests of effort-related choice behavior for assessing the effects of D1 agonists. Copyright © 2015. Published by Elsevier Inc.
    Full-text · Article · May 2015 · Pharmacology Biochemistry and Behavior
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    • "A variety of tasks have been used in rodents for assessing effort-related decision making, including operant tasks that offer animals choices between lever pressing for a more preferred food on ratio schedules or simply approaching and consuming a less preferred reinforcer (Salamone et al. 1991, 2002, 2007; Schweimer and Hauber 2005; Cagniard et al. 2006; Randall et al. 2012), effort discounting (Floresco et al. 2008; Bardgett et al. 2009), and a T-maze task that uses a vertical barrier to provide an effort-related challenge (Salamone et al. 1994; Cousins et al. 1996; Mott et al. 2009; Mai et al. 2012). Considerable evidence indicates that effortrelated decision making in rodents is regulated by a distributed circuit that includes mesolimbic dopamine (DA), prefrontal cortex, basolateral amygdala, nucleus accumbens, and ventral pallidum (Salamone et al. 1997, 2007; Walton et al. 2003; Cagniard et al. 2006; Floresco and Ghods-Sharifi 2007; Farrar et al. 2008; Mingote et al. 2008; Font et al. 2008; Hauber and Sommer 2009; Ghods-Sharifi and Floresco 2010; Salamone and Correa 2012; Nunes et al. 2013a). Recent studies have shown that conditions associated with depression, including stress (Shafiei et al. 2012), as well as the pro-inflammatory cytokine interleukin 1-β (Nunes et al. 2014), shift effortrelated choice behavior and reduce selection of the high effort alternative. "
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    ABSTRACT: Rationale Depressed people show effort-related motivational symptoms, such as anergia, retardation, lassitude, and fatigue. Animal tests can model these motivational symptoms, and the present studies characterized the effort-related effects of the vesicular monoamine transport (VMAT-2) inhibitor tetrabenazine. Tetrabenazine produces depressive symptoms in humans and, at low doses, preferentially depletes dopamine. Objectives The current studies investigated the effects of tetrabenazine on effort-based decision making using the T-maze barrier task. Methods Rats were tested in a T-maze in which the choice arms of the maze contain different reinforcement densities, and under some conditions, a vertical barrier was placed in the high-density arm to provide an effort-related challenge. The first experiment assessed the effects of tetrabenazine under different maze conditions: a barrier in the arm with 4 food pellets and 2 pellets in the no barrier arm (4-2 barrier), 4 pellets in one arm and 2 pellets in the other with no barrier in either arm (no barrier), and 4 pellets in the barrier arm with no pellets in the other (4-0 barrier). Results Tetrabenazine (0.25-0.75 mg/kg IP) decreased selection of the high cost/high reward arm when the barrier was present, but had no effect on choice under the no barrier and 4-0 barrier conditions. The effects of tetrabenazine on barrier climbing in the 4-2 condition were reversed by the adenosine A2A antagonist MSX-3 and the catecholamine uptake inhibitor and antidepressant bupropion. Conclusions These studies have implications for the development of animal models of the motivational symptoms of depression and other disorders.
    Full-text · Article · Oct 2014 · Psychopharmacology
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    • "Numerous studies have shown, for example, that hyperdopaminergic rats were willing to work more for identical amount of reward (Beeler et al., 2010; Cousins & Salamone, 1994; Salamone et al., 2005). The effective apparent " cost " of effort is bidirectionally modulated by manipulation of indirect D2 MSN activity: Pharmacological manipulations that enhance such activity result in more avoidance of effortful actions, whereas inhibition of this pathway has the opposite effect, decreasing the effective cost (Farrar et al., 2010, 2008; Mingote et al., 2008; Nunes et al., 2010). Neural models suggest that these effects are mediated by differential coding of positive and negative consequences of actions in distinct MSN populations, as observed in electrophysiological studies (Samejima et al., 2005). "
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    ABSTRACT: The striatal dopaminergic system has been implicated in reinforcement learning (RL), motor performance, and incentive motivation. Various computational models have been proposed to account for each of these effects individually, but a formal analysis of their interactions is lacking. Here we present a novel algorithmic model expanding the classical actor-critic architecture to include fundamental interactive properties of neural circuit models, incorporating both incentive and learning effects into a single theoretical framework. The standard actor is replaced by a dual opponent actor system representing distinct striatal populations, which come to differentially specialize in discriminating positive and negative action values. Dopamine modulates the degree to which each actor component contributes to both learning and choice discriminations. In contrast to standard frameworks, this model simultaneously captures documented effects of dopamine on both learning and choice incentive-and their interactions-across a variety of studies, including probabilistic RL, effort-based choice, and motor skill learning. (PsycINFO Database Record (c) 2014 APA, all rights reserved).
    Full-text · Article · Jul 2014 · Psychological Review
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