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Effort valuation-a process for selecting actions based on the anticipated value of rewarding outcomes and expectations about the work required to obtain them-plays a fundamental role in decision-making. Effort valuation is disrupted in chronic stress states and is supported by the anterior cingulate cortex (ACC), but the circuit-level mechanisms by which the ACC regulates effort-based decision-making are unclear. Here, we show that ACC neurons projecting to the nucleus accumbens (ACC-NAc) play a critical role in effort valuation behavior in mice. Activity in ACC-NAc cells integrates both reward- and effort-related information, encoding a reward-related signal that scales with effort requirements and is necessary for supporting future effortful decisions. Chronic corticosterone exposure reduces motivation, suppresses effortful reward-seeking, and disrupts ACC-NAc signals. Together, our results delineate a stress-sensitive ACC-NAc circuit that supports effortful reward-seeking behavior by integrating reward and effort signals and reinforcing effort allocation in the service of maximizing reward.
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http://dx.doi.org/10.1016/j.neuron.2023.10.020 | DOI Listing |
bioRxiv
June 2025
Department of Psychiatry and Behavioral Sciences, Stanford University, Stanford, CA 94305.
Effort is costly: given a choice, we tend to avoid it. But in many cases, effort adds value to the ensuing rewards. From ants to humans, individuals prefer rewards that had been harder to achieve.
View Article and Find Full Text PDFAddict Biol
May 2024
Department of Anesthesiology and Perioperative Care, School of Medicine, University of California, Irvine, Irvine, California, USA.
Opioid addiction is a relapsing disorder marked by uncontrolled drug use and reduced interest in normally rewarding activities. The current study investigated the impact of spontaneous withdrawal from chronic morphine exposure on emotional, motivational and cognitive processes involved in regulating the pursuit and consumption of food rewards in male rats. In Experiment 1, rats experiencing acute morphine withdrawal lost weight and displayed somatic signs of drug dependence.
View Article and Find Full Text PDFNat Commun
November 2023
Department of Neurobiology, University of Maryland School of Medicine, Baltimore, MD, USA.
Brain levels of the endocannabinoid 2-arachidonoylglycerol (2-AG) shape motivated behavior and nucleus accumbens (NAc) dopamine release. However, it is not clear whether mobilization of 2-AG specifically from midbrain dopamine neurons is necessary for dopaminergic responses to external stimuli predicting forthcoming reward. Here, we use a viral-genetic strategy to prevent the expression of the 2-AG-synthesizing enzyme diacylglycerol lipase α (DGLα) from ventral tegmental area (VTA) dopamine cells in adult mice.
View Article and Find Full Text PDFNeuron
February 2024
Feil Family Brain and Mind Research Institute, Weill Cornell Medicine, New York, NY 10021, USA; Department of Psychiatry, Weill Cornell Medicine, New York, NY 10021, USA. Electronic address:
Effort valuation-a process for selecting actions based on the anticipated value of rewarding outcomes and expectations about the work required to obtain them-plays a fundamental role in decision-making. Effort valuation is disrupted in chronic stress states and is supported by the anterior cingulate cortex (ACC), but the circuit-level mechanisms by which the ACC regulates effort-based decision-making are unclear. Here, we show that ACC neurons projecting to the nucleus accumbens (ACC-NAc) play a critical role in effort valuation behavior in mice.
View Article and Find Full Text PDFPsychopharmacology (Berl)
January 2024
Laboratory for Advanced Brain Functions, Institute for Protein Research, Osaka University, Suita, Osaka, Japan.
Rationale: Clozapine N-oxide (CNO) has been developed as a ligand to selectively activate designer receptors exclusively activated by designer drugs (DREADDs). However, previous studies have revealed that peripherally injected CNO is reverse-metabolized into clozapine, which, in addition to activating DREADDs, acts as an antagonist at various neurotransmitter receptors, suggesting potential off-target effects of CNO on animal physiology and behaviors. Recently, second-generation DREADD agonists compound 21 (C21) and JHU37160 (J60) have been developed, but their off-target effects are not fully understood.
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