Jennifer L. Bizon

Dopamine contributes to reward-related decision making, but its contributions to decision contexts that include explicit punishment are less well understood. To elucidate the role of ventral tegmental area (VTA) dopamine neurons in decision making under risk of punishment, we used fiber photometry to record activity in these neurons during a decision-making task in which rats choose between a small, “safe” reward and a large reward associated with varying probabilities of explicit punishment. Dopamine neuron activity exhibited phasic increases during risky “Wins” (reward without punishment) and phasic decreases during risky “Losses” (reward plus punishment), each of which scaled with punishment probability and intensity. Further analyses revealed that this outcome-evoked activity predicted choices on subsequent trials. To determine whether VTA dopamine neuron activity plays a causal role in these risk-based decisions, we used optogenetics to selectively inhibit these neurons during risky Wins and Losses. Inhibition of VTA dopamine neurons during Wins selectively reduced the frequency of risky choices after a Win, whereas inhibition during Losses selectively reduced the frequency of risky choices after a Loss. These data reveal that VTA dopamine neuron activity during outcome receipt is causally related to subsequent decision-making behavior. In addition, the fact that the effects of inhibition on choice behavior were specific to the outcome with which the inhibition was paired suggests that VTA dopamine neuron activity contributes to updating after Wins and Losses independently. Significance Statement: Dopamine is implicated in movement, motivation, and learning, and has been strongly linked with substance use and risk-seeking behavior. Despite these associations, it is unclear how the activity of dopamine neurons influences decision making under risk of punishment. To elucidate this, we recorded from ventral tegmental area (VTA) dopamine neurons and found that their activity at the population level integrates reward alongside the probability and intensity of punishment experienced during risky outcomes. Further, inhibition of VTA dopamine neuron activity during risky outcomes decreased risk-seeking behavior in an outcome-specific manner. Our findings align with models suggesting that VTA dopamine neurons signal prediction errors, and provide insight into the role of these neurons in adaptive decision making.

Aging is associated with chronic low-grade inflammation, which is thought to contribute to both cognitive decline and various neurodegenerative diseases. Cannabinoids are reported to reduce levels of inflammatory markers; however, these effects have not been thoroughly assessed in aged subjects. To address this gap, we evaluated effects of chronic cannabis smoke exposure on peripheral and brain inflammatory markers in young and aged mice. Young adult (4 months old) and aged (22 months old) C57Bl/6J mice were exposed to smoke from burning either cannabis (5.5 - 6.2% THC) or placebo (0% THC) cigarettes daily for 30 consecutive days. Following exposure sessions, both blood and brain tissue from the prefrontal cortex (PFC) and hippocampus (HPC) were collected and analyzed for multiple markers of inflammation. Overall, the patterns of inflammatory markers varied across the three tissue types. Both comparisons of individual cytokines and global cytokine profiles revealed that aging caused modest increases in cytokine levels in serum and PFC, with little influence of cannabis exposure. In contrast, HPC samples had stronger age effects, with numerous cytokines elevated in aged mice compared to young. Cannabis also interacted with age in the HPC such that smoke exposure tended to increase cytokine levels in young mice but decrease them in aged mice. These findings point to general age-related increases in brain inflammatory markers in this mouse strain, but cannabis effects were largely restricted to the HPC, where smoke exposure produced age-dependent changes in cytokine profiles. HIGHLIGHTS: Aged C57BL/6 mice have elevated cytokines levels, especially in the hippocampus Cannabis smoke exposure produces age-dependent changes in cytokine levels in hippocampus In HPC, cannabis smoke exposure attenuated age-related increases in IL-13 and Dkk1

The ability to choose adaptively between rewards differing in magnitude and delay (intertemporal choice) is critical for numerous life outcomes. Compared to younger adults, older adults tend to exhibit greater preference for large, delayed over small, immediate rewards (ie less delay discounting), which could lead to missed opportunities to obtain resources necessary for quality of life. Intertemporal choice is mediated by the prefrontal cortex, but how this is impacted by advanced age is not well understood. We used optogenetic inactivation to investigate contributions of medial prefrontal cortex (mPFC) during distinct components of an intertemporal choice task in young and aged rats. mPFC inactivation during deliberation (during decisions between small, immediate vs. large, delayed rewards) increased preference for large, delayed rewards in both age groups. In contrast, inactivation during delays prior to large reward delivery increased preference for large, delayed rewards only in aged rats. Choices were unaffected by inactivation during other task phases. Results suggest that mPFC integrates information regarding anticipated outcomes into the decision process across the whole lifespan, but that only in aging is mPFC critical for consolidating information regarding reward delays into the decision structure in order to modulate choice behavior.

There are few cognitive functions more essential than decision making, as better decisions improve our chances of survival. Cost–benefit decisions as they apply to most scenarios in the developed world can range from relatively mundane to reasonably important; however, particularly risky choices such as speeding on our way to work or consuming suspicious foods can pose a genuine risk of significant harm or illness. How is it that our brains learn and evaluate these risks and rewards to arrive at decisions? Additionally, what drives some of us to continue despite, or avoid because of, potential adverse consequences? This review explores neural mechanisms underlying cost–benefit decision making, focusing on paradigms used in human and particularly rodent studies to model decision making under the risk of explicit punishments, such as pain, discomfort, or loss. The review focuses on several key brain regions (the prefrontal cortex, basolateral amygdala, and striatum), and their roles in the assessment of rewards, punishments (or risk thereof), and motivated behaviors. It also discusses pertinent literature on the role of dopamine arising from the ventral tegmental area, as a neuromodulator critical for learning and reinforcement in the context of risky decision making.This article is categorized under: Neuroscience > Behavior Economics > Individual Decision‐Making Psychology > Reasoning and Decision Making

The neuropeptide oxytocin is traditionally known for its roles in parturition, lactation, and social behavior. Other data, however, show that oxytocin can modulate behaviors outside of these contexts, including drug self-administration and some aspects of cost-benefit decision making. Here we used a pharmacological approach to investigate the contributions of oxytocin signaling to decision making under risk of explicit punishment. Female and male Long-Evans rats were trained on a risky decision-making task in which they chose between a small, "safe" food reward and a large, "risky" food reward that was accompanied by varying probabilities of mild footshock. Once stable choice behavior emerged, rats were tested in the task following acute intraperitoneal injections of oxytocin or the oxytocin receptor antagonist L-368,899. Oxytocin dose-dependently reduced preference for the large, risky reward only in females, whereas L-368,899 dose-dependently reduced preference for the large, risky reward in both sexes. Control experiments showed that these effects could not be accounted for by drug-induced alterations in preference for the large reward or shock sensitivity. Together, these results reveal partially sex-dependent effects of oxytocin signaling on risky decision making in rats. (PsycInfo Database Record (c) 2025 APA, all rights reserved).

Rationale With increasing legalization of recreational and medical cannabis, use of this drug is growing rapidly among older adults. As cannabis can impair cognition in young adults, it is critically important to understand how its consumption interacts with the cognitive profile of aged subjects, who are already at increased risk of decline. Objectives The current study was designed to determine how cannabis influences multiple forms of cognition in young adult and aged rats of both sexes when delivered via two translationally-relevant routes of administration. Methods Rats were exposed acutely to cannabis smoke or chronically to oral Δ9-tetrahydrocannabinol (Δ9THC), followed by cognitive testing. Results Acute cannabis smoke enhanced prefrontal cortex-dependent working memory accuracy in aged males, but impaired accuracy in aged females, while having no effects in young adults of either sex. In contrast, the same cannabis smoke regimen had minimal effects on a hippocampus-dependent trial-unique non-matching to location mnemonic task, irrespective of age or sex. Chronic oral consumption of Δ9THC enhanced working memory in aged rats of both sexes, while having no effects in young adults. In contrast, the same Δ9THC regimen did not affect spatial learning and memory in either age group. Minimal age differences were observed in Δ9THC pharmacokinetics with either route of administration. Conclusions The results show that cannabis and Δ9THC can attenuate working memory impairments that emerge in aging. While these enhancing effects do not extend to hippocampus-dependent cognition, cannabis does not appear to exacerbate age-associated impairments in this cognitive domain.

With increased legalization of recreational and medical cannabis, use of this drug is growing rapidly among older adults. As cannabis use can impair cognition in young adults, it is critically important to understand how consumption interacts with the cognitive profile of aged individuals, who are already at increased risk of decline. The current study was designed to determine how cannabis influences multiple forms of cognition in young adult and aged rats of both sexes when delivered via two translationally-relevant routes of administration. Acute exposure to cannabis smoke enhanced prefrontal cortex-dependent working memory accuracy in aged males, but impaired accuracy in aged females, while having no effects in young adults of either sex. In contrast, the same cannabis smoke exposure regimen had minimal effects on a hippocampus-dependent trial-unique non-matching to location mnemonic task, irrespective of age or sex. In a second set of experiments, chronic oral consumption of Δ9-tetrahydrocannabinol (Δ9THC) enhanced working memory in aged rats of both sexes, while having no effects in young adults. In contrast, the same oral Δ9THC regimen did not affect spatial learning and memory in either age group. Minimal age differences were observed in Δ9THC pharmacokinetics with either route of administration. Together, these results show that cannabis and Δ9THC can attenuate working memory impairments that emerge in aging. While these enhancing effects do not extend to hippocampus-dependent cognition, cannabis does not appear to exacerbate age-associated impairments in this cognitive domain.

The neuropeptide oxytocin is traditionally known for its roles in parturition, lactation, and social behavior. Other data, however, show that oxytocin can modulate behaviors outside of these contexts, including drug self-administration and some aspects of cost-benefit decision making. Here we used a pharmacological approach to investigate the contributions of oxytocin signaling to decision making under risk of explicit punishment. Female and male Long-Evans rats were trained on a risky decision-making task in which they chose between a small, “safe” food reward and a large, “risky” food reward that was accompanied by varying probabilities of mild footshock. Once stable choice behavior emerged, rats were tested in the task following acute intraperitoneal injections of oxytocin or the oxytocin receptor antagonist L-368,899. Neither drug affected task performance in males. In females, however, both oxytocin and L-368,899 caused a dose-dependent reduction in preference for large risky reward. Control experiments showed that these effects could not be accounted for by alterations in food motivation or shock sensitivity. Together, these results reveal a sex-dependent effect of oxytocin signaling on risky decision making in rats.