Article Figures & Data
Figures
- Fig. 1.
Effort-related choice tasks conducted in rodent operant boxes and mazes (see cited references in text for details). Left: The concurrent lever-pressing/chow-feeding choice tasks give animals the option of lever pressing on a fixed or progressive ratio schedule to obtain access to preferred high-carbohydrate pellets versus approaching and consuming freely available chow. Right: The T-maze barrier choice task presents trials that allow animals to select one arm that requires them to climb a vertical barrier to obtain a large magnitude of reinforcement versus the other arm, which has no barrier and a lower magnitude of reinforcement.
- Fig. 2.
Anatomic circuit diagrams depicting some of the brain structures and neurotransmitters involved in studies of effort-related decision making in rodents. Left: Schematic of the rat brain showing mesostriatal DA systems. Mesolimbic DA projection is shown with the solid arrow, whereas nigrostriatal DA projections are illustrated with dotted line. Right: This figure is a circuit diagram illustrating the limbic, cortical, striatal, and pallidal connections that are involved in effort-based choice. Furthermore, this figure illustrates the results from a group of studies employing disconnection methods. With these procedures, researchers produce combined contralateral damage to interconnected brain structures to determine whether they form part of a serial circuit that participates in a particular behavioral function (Floresco and Ghods-Sharifi, 2007: basolateral amygdala and anterior cingulate cortex; Hauber and Sommer, 2009: anterior cingulate cortex and nucleus accumbens core; Mingote et al., 2008: nucleus accumbens core and lateral ventral pallidum).
- Fig. 3.
Effects of the adenosine A2A antagonist preladenant (PL) on effort-related choice behavior. (A and B) Ability of the adenosine A2A antagonist preladenant to reverse the effects of tetrabenazine (TBZ) in rats responding on the concurrent FR5/chow choice task. All rats (n = 13; adult male, Sprague–Dawley rats; Harlan Sprague–Dawley, Indianapolis, IN) were trained on the FR5/chow-feeding choice procedure, as described in Yohn et al. (2016b,d,e), and tested in 30-minute sessions. Rats were tested 5 days per week, and, after several weeks of training, drug testing was conducted 1 day each week, with a randomized order of drug treatments. All animals received intraperitoneal (IP) injections of vehicle or 0.75 mg/kg tetrabenazine 120 minutes prior to testing, and also received IP injections of vehicle or preladenant IP (0.05, 0.1, 0.2 mg/kg) 25 minutes prior to testing. (A) Lever pressing. Mean (± S.E.M.) number of lever presses in the 30-minute session are shown. There was an overall significant effect of drug treatment on lever pressing [F(4,48) = 12.0, P < 0.001]. Planned comparisons showed that TBZ significantly decreased lever pressing compared with vehicle (#P < 0.05), and that all doses of preladenant plus TBZ significantly increased lever pressing relative to TBZ plus vehicle (*P < 0.01). (B) Chow intake. Mean (± S.E.M.) gram quantities of chow intake are shown. There was an overall significant effect of drug treatment on chow intake [F(4,48) = 7.43, P < 0.001]. Planned comparisons showed that TBZ significantly increased chow consumption relative to vehicle (#P < 0.05), and that all doses of preladenant plus TBZ significantly decreased chow intake relative to TBZ plus vehicle (*P < 0.01). (C and D). Effect of preladenant in rats responding on the PROG/chow-feeding choice task. The rats that were used for the FR5/chow-feeding experiment (n = 13) were then trained on the concurrent PROG/chow-feeding choice task, as described by Yohn et al. (2016a). Rats were tested 5 days per week, and, after several weeks of training, drug testing was conducted 1 day each week, with a randomized order of drug treatments. All animals received IP injections of vehicle or preladenant IP (0.1, 0.2, 0.4 mg/kg) 25 minutes prior to testing. (C) Lever pressing. Mean ± S.E.M. number of lever presses in the 30-minute session is shown. There was an overall significant effect of drug treatment on PROG lever pressing [F(3,36) = 3.7, P < 0.05]. Planned comparisons showed that the highest dose of preladenant (0.4 mg/kg) significantly increased lever pressing relative to vehicle (*P < 0.05). (D) Chow intake. Mean (± S.E.M.) gram quantities of chow intake are shown. The overall tendency of preladenant administration to decrease chow intake approached statistical significance [F(3,36) = 2.63, P = 0.065]. [All results from this figure were presented at the 2017 Society for Neuroscience meeting (Rotolo et al., 2017).]
In this issue
Pharmacology of Effort-Related Aspects of Motivation
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- Article
- Abstract
- I. Introduction: Motivational Processes and Psychopharmacology
- II. Neural Circuits and Transmitters Mediating Effort-Based Choice: Mesolimbic Dopamine
- III. Behavioral Effects of Dopaminergic Manipulations on Effort-Related Tasks Are Not Due to Broad or General Changes in Reward, Temporal Processing, or Motor Incapacity
- IV. What Fundamental Processes Underlie the Low-Effort Bias Induced by Interference with Dopamine Transmission?
- V. Neural Circuits and Transmitters Mediating Effort-Based Choice: Adenosine, GABA, and Nondopaminergic Components of the Circuit
- VI. Clinical Implications: Targeting Drugs for the Potential Treatment of Effort-Based Dysfunctions
- VII. Conclusions
- Authorship Contributions
- Footnotes
- Abbreviations
- References
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