Behavioral Neuroscience
● American Psychological Association (APA)
Preprints posted in the last 90 days, ranked by how well they match Behavioral Neuroscience's content profile, based on 25 papers previously published here. The average preprint has a 0.01% match score for this journal, so anything above that is already an above-average fit.
Palmer, J. A.; Chavez Lopez, K.; Laubach, M.
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Studies of visual discrimination in rodents can confound the effects of cue salience with reward value, making it difficult to determine which factor guides choice behavior. We examined this issue by testing how changes in relative salience affect decision dynamics in rats performing a two-alternative forced-choice task in which rats chose between visual cues associated with high or low sucrose rewards. After initial training with high and low luminance cues, we introduced a novel cue of intermediate luminance as a "luminance shift" test. The intermediate luminance cue substituted for either the brighter or dimmer cue and had the same reward value as the cue that it replaced. We found that while rats maintained a preference for the higher-value option, the introduction of a perceptually more similar cue consistently reduced choice preference and eliminated latency differences compared to baseline. Using drift diffusion modeling, we determined that the luminance shifts primarily caused a reduction in the drift rate (the speed of evidence accumulation), reflecting increased difficulty in cue discrimination. This finding suggests that the relative salience of the options determines the efficiency of evidence accumulation in value-based decisions. Furthermore, this effect on drift rate shows a dissociation from our previous work (Palmer et al., 2024), where prefrontal cortex inactivation specifically affected only the decision threshold. Our results demonstrate that relative salience influences deliberation, with low-level perceptual features shaping the computational dynamics of value-based choice. Our findings clarify the distinct contributions of sensory input and prefrontal function in the decision process. Significance StatementThis study reveals that changes in the relative salience of visual stimuli shape the computational dynamics of value-based decisions. We trained rats to make visually guided choices and found that relative differences in the brightness of the stimuli affect how quickly the rats made decisions and how often they chose a higher-value option. Our findings, together with a recent study on the role of the prefrontal cortex in value-guided decisions (Palmer et al., 2024), suggest that separate factors influence choice dynamics in rodents: visual salience affects the speed of deliberation, while prefrontal activity regulates caution. This study helps clarify how sensory and higher cognitive variables relate to the distinct computational components of the decision process.
Roy, D. J.; Burton, T. J.; Balleine, B.
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Considerable evidence suggests that the motivational control of instrumental action depends on incentive learning; i.e., on the opportunity to learn how the value of the consequences or outcome of an action, (e.g., a specific food) varies under different motivational conditions (e.g., under different degrees of hunger). The current study investigated whether learning the values of high-protein and high-carbohydrate rewards under different degrees of protein and carbohydrate appetite is also necessary for these nutrient-specific appetites to exert control over instrumental performance. Experiment 1 gave differing consummatory experience to whey protein and polycose carbohydrate outcomes under protein and carbohydrate appetite and found that, without the opportunity for incentive learning, the performance of actions earning these outcomes was insensitive to a shift in appetite. However, once the opportunity for incentive learning was provided, the rats increased their instrumental performance on a lever that earned the whey outcome relative to the polycose lever when protein hungry and on the polycose lever relative to the whey lever when carbohydrate hungry. Experiment 2 assessed how these nutrient-specific states exerted this control; whether, once learned, nutrient values were immediately controlled by nutrient appetite or whether this was based on conditional control acquired during experience with the outcomes under different nutrient appetites. We found that exposure to an outcome under a single nutrient-specific state was not sufficient to establish state-specific control. Instead, establishing the conditional control of outcome value required exposure to both the whey and polycose outcomes under both protein and carbohydrate appetites.
Galvan, K. J.; Grijalva Torres, S. D.; Powers, R. E.; Calvo, D. E.; Moschak, T. M.
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The motivation to pursue drugs is a fundamental element of substance use. Different tasks assess motivation in the face of effort, punishment, or the absence of the drug, and recent studies have suggested that a shared latent variable may drive behavior across these tasks. The prelimbic cortex (PL) is implicated in these behaviors, but it is unknown if its role is driven by shared or distinct neural ensembles. We recorded PL activity using in vivo endoscopic calcium imaging in 32 male and female Sprague-Dawley rats as they completed cocaine or water self-administration, extinction, progressive ratio, and punished self-administration. We found that behavior across tasks was driven by a single latent variable in water, but not cocaine rats. We also found distinct neural populations that tracked reward pursuit. We found that one population of cost-sensitive neurons had significantly fewer neurons present during the progressive ratio task. A second population of reward-sensitive neurons had significantly fewer neurons present during the extinction task. Individual rats with more of these neurons present during the task had significantly higher levels of reward pursuit in the progressive ratio and extinction tasks, respectively. Furthermore, this relationship was true across cocaine and water rats, suggesting a general role in motivation independent of reward type. When we examined whether shared patterns of neural activity predicted shared patterns of behavior across the tasks, we found no relationships. Thus, our findings suggest that distinct facets of reward motivation are tracked by distinct ensembles in the PL, rather than a shared ensemble.
Madhuranthakam, I. M.; Ahmed, S.; Basak, K.; Uddin, A.; Tumpa, M. A. A.; Jimenez, A. M.; Cherry, R.; Rodriguez, A.; Chowdhury, M.; Keck, T. M.; Job, M. O.
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BackgroundSex differences in psychostimulant-related behaviors are often attributed to biological sex; however, individual variability may also strongly influence behavioral outcomes. The new MISSING (Mapping Intrinsic Sex Similarities as an Integral quality of Normalized Groups) model identifies mixed-sex behavioral groups in which differences are driven primarily by individual variability rather than sex. The goal of this study was to validate the MISSING model for psychostimulant/sucrose self-administration. MethodsLong Evans rats self-administered methamphetamine (METH, male n = 25, female n = 32, 0.1 mg/kg/infusion, FR1, 6h per day for 20 days), sucrose (male n = 20, female n = 22, one-20 mg pellet/delivery, all other conditions being equal) and saline (male n = 3, female n = 10, other things being equal). We developed a new Quantitative Structure of Curve Analytical (QSCAn) model (using exponential-plateau and linear fit) for the assessment of individual drug self-administration time curve profiles irrespective of biological sex. We analyzed our data using regression analysis and ANOVA. ResultsQSCAn identified three distinct self-administration profiles (consisting of both sexes), which we named exponential-plateau negative (EP-), exponential-plateau positive (EP+), and undefined (EP0). There were no differences in self-administration profiles when we compared males and females within the same group. Differences between sexes (when observed) were due to mismatched comparisons (males from one group versus females from a different group). ConclusionsOur study reinforces the MISSING model for psychostimulant and sucrose self-administration by indicating that differences between males and females (when observed) may not necessarily be driven by biological sex. Significance StatementCurrent approaches often interpret variability in psychostimulant self-administration between males and females primarily through the lens of biological sex. However, this framework may overlook meaningful behavioral phenotypes shared across sexes. The present quantitative model suggests that individual patterns of behavior may better account for variability than sex alone, particularly in behaviors not strongly driven by sex-hormone-dependent mechanisms such as drug self-administration. By classifying animals according to behavioral profiles rather than biological sex, this approach may foster the identification of clinically and biologically relevant phenotypes underlying psychostimulant reinforcement.
Payne, K.; Ruble, S.; Ness, H.; Durrett, H.; Kramer, C.; Diehl, M. M. M.
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The platform-mediated active avoidance (PMA) task has been used as a rodent model of decision-based active avoidance in which rat learn to avoid a tone-signaled shock. Prior studies utilizing the PMA task have primarily investigated avoidance, freezing, and food-seeking behaviors, but few studies have thoroughly assessed darting behavior, a more recently identified measure of fear that has been largely explored in conditional fear paradigms. Here, we investigated the properties of darting that occur during the PMA task, in which rats either acquired the PMA task alone or with a social partner. We found that rats undergoing solitary PMA produced significantly more darting bouts, whereas rats undergoing social partner PMA produced darts that were faster and shorter in duration. We also found that darting in solitary PMA was predominantly concentrated at the platform, whereas darting in social partner PMA occurred more often outside of the platform and lever zones. Analysis of darting trajectories, which included movements surrounding each darting bout, revealed that darting was embedded in a broader movement strategy between the platform and lever zones, especially during solitary PMA, and this pattern increased across training days. These findings suggest that darting during the PMA task serves as a learned strategy to navigate between reward and safety and is modulated by social context, which is distinct from escape-like darting observed in auditory fear conditioning.
Edwards, L. H.; Papanikolaou, L. F.; Wilson, M. R.; Brody, M. V.; Wade, W. F.; Cutler, M.; Arora, S. A.; Stratmann, A.; Canuelas del Valle, S.; Grella, S. L.
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Relapse-prevention strategies aimed at reducing relapse following abstinence, primarily focus on reducing cravings that lead to drug-seeking triggered by stress, drug-related cues, or re-exposure to the drug. Because addictive drugs form persistent associative contextual memories, we investigated how reactivation of cocaine-related hippocampal memories influences subsequent drug-seeking. Here, we tagged dorsal dentate gyrus (dDG) memory ensembles involved in encoding either a first or fourth cocaine exposure (15mg/kg, i.p) in male and female c57BL/6 mice using a TetTag approach. Mice underwent cocaine conditioned place preference (CPP), extinction, and reinstatement. We assessed whether optical reactivation of tagged cocaine-related ensembles could substitute for a cocaine priming injection to reinstate CPP, whether reactivation altered cocaine-induced reinstatement, and if these effects differed depending on stage of drug exposure. We also compared these effects to reactivation of saline-associated ensembles. Cocaine produced robust locomotor activation during conditioning, and sensitization developed across repeated drug exposures. Reactivation of a cocaine-related engram alone did not reinstate CPP. However, reactivation of the first cocaine exposure engram attenuated cocaine-induced reinstatement. In contrast, reactivation of the fourth exposure engram did not confer this protective effect. Interestingly, reactivation of saline-associated ensembles also reduced cocaine-induced reinstatement specifically in females, suggesting dDG ensemble reactivation may modulate relapse-related behavior through interference or neuromodulatory disruption of cocaine-associated representations, consistent with our prior work. These findings raise the possibility that early contextual experiences form competing or destabilizing representations that interfere with later cocaine-seeking when reactivated. Females also displayed greater sensitivity to locomotor-inducing effects of cocaine memory reactivation, although this was dissociated from CPP. Together, these findings show that cocaine memories are distinct across drug experience and selective reactivation of dDG engrams can differentially influence drug-seeking.
Lorenzo Gonzalez, A. P.; Allen, T. A.
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Interval timing (IT) is the ability to time events in the range from seconds to a few minutes, allowing animals to organize behavior in time at short durations. IT relies on two cognitive functions: 1) Measuring the passage of time; 2) Storing and retrieving temporal memories in a context appropriate manner. The hippocampus (HC) and medial prefrontal cortex (mPFC) have been shown critical to the accuracy and precision of time-contingent instrumental responses in IT. The anatomy supporting mPFC-HC interactions, required for memory encoding and retrieval, include projections from HC to mPFC, and indirect bidirectional connections through the ventral midline thalamus (VMT), most notably reuniens. Here, we explored VMTs role in retrieving fixed-interval (FI) temporal memories. Rats were trained on a 5s FI signaled by an auditory cue and demonstrated temporal memory by poking predominantly at the time of the expected reward. Timing responses on individual trials were classified into on-time, early, and random response. Across sessions, random response trials decreased following training. Next, we switched training to longer intervals (20s or 80s; daily sessions for weeks). To probe the role of the VMT in temporal memory retrieval, we infused the GABAA-agonist muscimol, or saline, before training sessions. Results show that VMT muscimol infusions decreased timing precision. Also, at both intervals, the number of on-time response trials decreased, and the number of random response trials significantly increased. The number of early response trials had no significant change at 20s, and significantly decreased at 80s. Overall, our results suggest that the VMT is critical for precise retrieval of temporal memories. We also describe per-trial response patterns with characteristics consistent across all trained intervals, suggesting multiple behavioral strategies at play during interval timing.
Troha, R.; Burks, D.; Petro, A.; Kirkpatrick, K.; Newman, E.
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Spatial memory is crucial for navigation and adapting to changing environmental conditions. Known neurophysiological mechanisms of spatial memory center on the importance of hippocampal activity and its spatial tuning. Yet, the behavioral strategies that support adaptive spatial encoding remain poorly understood. We have shown that dorsal hippocampal activity during rearing is necessary for spatial working memory, highlighting a role of information seeking behaviors for spatial memory encoding. Similarly, spatial tuning by dorsal hippocampal neurons is substantially updated during another information seeking behavior: attentive head scanning. However, the functional relationship between these behaviors is unknown. Here, to assess the relevance of environmental context for the expression of these behaviors, we quantified rearing and head scanning in a radial-arm-maze spatial working memory task while manipulating the height of the maze walls. Our goal was to test whether the stereotyped patterns of rearing that rats generate with tall walls are replaced with attentive head scanning when the walls are short enough to reach the top without rearing. We found that rats reared significantly less often when the walls were shortened and, instead, exhibited frequent attentive head scanning. The head scanning was done when and where the rats had previously exhibited stereotyped rearing. These results support the hypothesis that rearing and head scanning are functionally related behaviors. Future work should test two key inferences: 1) Head scanning is a critical epoch of spatial memory encoding, and 2) Spatial tuning by hippocampal neurons is updated during rearing. Significance statementSpatial memory is a core cognitive function, essential for healthy independent living. Though the hippocampus is critical for spatial memory, it remains unclear when and how. Separate prior studies link rearing and lateral head scanning to key periods of hippocampal processing, suggesting both behaviors support sensory information gathering for updating cognitive maps. However, their relationship is unresolved. Here, we test whether these behaviors are functionally interchangeable, with environmental structure determining expression. In a radial-arm maze, rats reared frequently with 21 cm walls but showed reduced rearing when walls were shortened to 4.6 cm, instead increasing head scanning at similar locations. These findings suggest rearing and head scanning share underlying motivations and provide a basis for comparing hippocampal activity during exploration.
Dai, Y.; Castillo, K.; Hinman, J. R.
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Hormonal regulation of patch-leaving decision-making remains poorly understood. Here, young adult male and female Long-Evans rats were tested in a patch-leaving task before and after orchiectomy (ORCH), ovariectomy (OVX), or sham surgery, and were subsequently assessed in an impulsive-choice task. Patch leaving was measured under long- and short-travel conditions. Before surgery, males showed longer overstay than females during long-travel sessions, whereas no clear sex difference was detected during short-travel sessions. After surgery, orchiectomy did not produce a uniform shift in patch leaving but selectively disrupted the progressive reduction in overstay that normally emerged across repeated long-travel sessions. By contrast, ovariectomy produced weaker effects and did not reveal a comparably robust change in female patch leaving. Spatial and idle occupancy analyses showed that gonadectomy also altered within-patch behavior, with orchiectomy most strongly increasing idling-related measures in males, whereas ovariectomy more strongly redistributed female patch occupancy. Estrous stage did not significantly organize pre-surgical female overstay. Greater impulsive choice was associated with smaller post-surgical reductions in long-travel overstay in the unadjusted analysis. Together, these findings indicate that testicular hormones selectively support patch-leaving adaptation under high travel cost.
Lee, J.
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RationaleAppetitive Pavlovian cues can drive maladaptive reward seeking via stimulus-reward memories. Disrupting memory reconsolidation offers a potential strategy to reduce their influence, but evidence for {beta}-adrenergic blockade with propranolol is inconsistent across behavioural paradigms, particularly relative to NMDA receptor antagonism. ObjectivesWe tested whether propranolol disrupts reconsolidation of appetitive sucrose memories in a discriminative goal-tracking paradigm, and compared its effects with those of the most commonly used NMDA receptor antagonist, MK-801. MethodsAdult Lister hooded rats underwent discriminative Pavlovian conditioning. Thirty minutes before a brief memory reminder (non-reinforced or reinforced), rats received systemic drug treatment or saline control. In study 1, MK-801 (0.1 mg/kg) was administered to male rats. In study 2, propranolol (10 mg/kg) was administered to equal numbers of male and female rats. Goal-tracking was tested drug-free at 1 and 8 days. ResultsIn study 1, MK-801 impaired subsequent discriminated responding at test. These effects were observed not only when reminder was non-reinforced as in previous successful demonstrations, but also with reinforced reminder. In study 2, Propranolol also impaired subsequent goal-tracking, regardless of reminder type, and the effects were consistent across sexes. ConclusionsPropranolol can disrupt reconsolidation of appetitive goal-tracking memories to a similar extent as MK-801 under conditions that promote memory destabilisation. These findings demonstrate that {beta}-adrenergic blockade can impair appetitive memory reconsolidation in a goal-tracking paradigm, challenging prior null findings and revitalising the potential for propranolol-based interventions in maladaptive reward-seeking behaviours.
Perez, O. D.; Cancino, N.; Hermosilla, D.; Soto, F. A.; Vogel, E. H.
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In animal learning research, learning is often represented by plotting a behavioral measure as a function of training trials. A particularly clear case is habituation, a basic form of learning in which repeated presentation of a stimulus produces a decrement in responding. Although retention tests provide the strongest basis for evaluating durable habituation once short-lived performance effects have dissipated, the pattern of response change across stimulus repetitions, or habituation curve, remains theoretically and empirically relevant because it is used to characterize determinants of habituation, individual and clinical profiles, and functional forms, including linear, curvilinear, asymptotic, and mixed incremental-decremental patterns of responding. However, group averaged curves may conceal substantial individual heterogeneity. Here, we analyzed archived human eyeblink habituation data from 157 participants to ask whether the curve shape selected for the group average reflects the curve shapes observed at the individual level. Five candidate functions were fitted separately to each participant and to the corresponding group average. No single function characterized most individuals. More importantly, the model selected for the group average differed from the most frequent individual model in all four groups. When data were pooled across groups, the average favored a dual-process form, a shape that matched the individual plurality in none of them. Simulation analyses showed that averaging heterogeneous individual trajectories can itself produce a group curve that favors a more complex model. Our findings show that group averaged habituation curves should not be treated as direct descriptions of the typical individual trajectory.
Cook, J. N.; Gevorgyan, M.; Armitage, J.; Jones, J.
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The circadian system is an important regulator of reward-related neural function and behavior. Dopamine (DA) release in the nucleus accumbens is a key component of reward processing, yet how circadian timing shapes DA release in relation to reward behavior remains unclear. Here, we investigated circadian rhythms in DA release and reward behavior using long-term fiber photometry paired with an automated reward delivery and measurement system. We found two distinct circadian rhythms in DA release: spontaneous DA, reflecting ongoing DA release not associated with reward, and reward-evoked DA, reflecting transient DA response during reward. Spontaneous DA peaked during the early subjective day, whereas reward-evoked peak DA peaked near the day-to-night transition. Both rhythms were distinct from reward behavior, which peaked during the early subjective night. Linear modeling further showed that the relationship between reward-evoked DA and reward behavior depended on circadian time, with greater DA responses occurring between late subjective day and early subjective night. Spontaneous baseline and reward-evoked DA were also negatively correlated, and this relationship was likewise modulated across circadian time. Together, these findings support a model in which circadian modulation of baseline DA may alter the gain of reward-evoked signaling, amplifying DA responses across behaviorally relevant times of day.
Hodges, C. I.; Duffy, E. P.; Ward, J. O.; Hale, L. H.; Andrews, C.; Saba, L. M.; Ehringer, M. A.; Bachtell, R. K.
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Opioid Use Disorder (OUD) remains a prominent threat to global health. Genetic background influences the susceptibility of developing OUD, although specific genetic factors remain elusive. Rodent models that differ in susceptibility to escalation and dysregulation of opioid use are valuable tools to facilitate discovery of genetic pathways. Phenotypes associated with the development of OUD were compared in seven classic inbred rat strains (M520/N, WKY/NCrl, F344/NCrl, F344/Stm, LEW/Crl, LEW/SSNHsd, LE/Stm) from the Hybrid Rat Diversity Panel (HRDP). A two-phase self-administration paradigm was utilized to assess characteristics of the acquisition of oxycodone self-administration during daily 2-h sessions, and the escalation of oxycodone use during daily 12-h sessions. Genetic background influenced the acquisition of oxycodone self-administration as indicated by differences in the initiation of responding for oxycodone during each session and different amounts of oxycodone intake. We observed that escalation of oxycodone intake between-sessions was strain dependent, and the within-session distribution of oxycodone intake was strongly influenced by strain. The M520/N strain engaged in a unique pattern of intake, characterized by rapid initiation of oxycodone responding during the acquisition phase and a significant burst-like responding during escalation. Strain-dependent sex differences were also observed in several acquisition and escalation metrics. Of interest, burst responding was more prevalent in females of the M520/N strain compared to males. Together, these data indicate that genetic background influences not only overall oxycodone intake, but specific within- and between-session metrics that capture patterns of consumption across the substance use trajectory.
Mahmoudi, M.; Gladding, J.; Kendig, M. D.; Castorina, A.; Turner, K.; Soegyono, O.; Bradfield, L. A.
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Relapse after treatment for various mental health disorders has been linked to tendency for reductions in responding to increase over time or following re-exposure to motivating stimuli. Here we show that, in rats, responding reduced through non-contingent outcome delivery does not recover in these ways, and that this learning depends on an intact lateral orbitofrontal cortex. These findings suggest that contingency degradation overwrites original learning which may support the development of relapse-resistant behavioural interventions.
Herring, E. W.; Hafenbreidel, M.; Patel, E. D.; Kupelian, P.; Syamala, T.; Zeng, S.; Torregrossa, M. M.; Morrison, S. E.
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Across species, adolescence is a time of heightened reward sensitivity and enhanced impulsivity and risk-taking. In adults, these behavioral features are linked with a tendency to approach and interact with reward-associated cues - a behavior known as sign tracking - which is thought to reflect the transfer of incentive salience from reward to cue. Counterintuitively, adolescents are less likely to exhibit sign tracking, compared with adults, and more likely to exhibit goal tracking, or approach to the site of reward. To investigate a possible neural basis for this age difference, we recorded the activity of individual neurons in the nucleus accumbens (NAc) of male and female rats during Pavlovian conditioning in adolescence and adulthood. In a separate group, we used a fluorescent indicator (GRABDA) to measure dopamine release at the same ages. We found that cue-evoked NAc activity increased over the course of training in adolescents and then further in adulthood. The majority of adolescents were goal trackers or intermediates, for whom reward-evoked activity peaked during adolescence and declines in adulthood, correlating with increased prevalence and intensity of sign tracking. Meanwhile, cue-evoked dopamine release was markedly higher in sign trackers than in goal trackers at all time points. These results suggest that the progression from adolescence to adulthood may be accompanied by changes in the engagement of the mesolimbic dopamine system and/or the responsivity of NAc neural signaling to dopamine, contributing to limited sensitivity to reward cues, coupled with heightened sensitivity to primary rewards, in adolescent animals. Significance StatementAdolescence is a time of enhanced reward sensitivity, impulsivity, and risk-taking, making adolescents vulnerable to drug use and other risky behaviors. In adults, attraction to reward-associated cues - which can be modeled in animals using a behavior called sign tracking - plays an important role in risky behaviors. Surprisingly, we find that adolescents exhibit less sign tracking compared with adults. Here, we investigate the neural circuits underlying this age difference by monitoring neural activity and dopamine release in the nucleus accumbens (NAc), a key brain area for reward-seeking behavior, in the same animals as adolescents and as adults. We find that the majority of adolescents show a reduced neural sensitivity to reward cues, but a heightened neural response to the reward itself.
Seib, D. R.; Liu, M. Q.; Tobiansky, D. J.; Floresco, S. B.; Soma, K. K.
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Voluntary physical activity is a highly motivated behavior with important implications for physical and mental health, yet the neural and endocrine mechanisms underlying motivation to exercise remain poorly understood. In contrast, motivation for sugar/palatable foods, drugs, and sex has been extensively characterized using operant paradigms. Here, we describe a novel progressive ratio operant task to measure motivation to run, independent of running ability. Using female Long Evans rats, which exhibit robust voluntary running behavior, we validated this paradigm by applying a manipulation well known to enhance the motivation to run: calorie restriction. Calorie-restricted animals exhibited increased operant responding to gain access to a running wheel, thus demonstrating heightened motivation for exercise. More specifically, calorie-restricted rats completed more ratios, reached a higher breakpoint in the progressive ratio task, ran more, and spent more time in the operant chamber. We did not observe any effects of calorie restriction on the estrous cycle or steroids (e.g. corticosterone, testosterone) in the blood or brain. Importantly, our task dissociates the motivational drive for physical activity from the ability to perform the physical activity itself, providing a new paradigm for studying the neural and endocrine mechanisms that regulate exercise motivation.
Chen, H.; Leng, S.; Khanam, S.; Mulligan, M. K.; Redei, E. E.
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Risk for opioid use disorder (OUD) is substantially heritable, yet its genetic architecture remains only partly understood. This study examined oxycodone intake in two nearly isogenic rat strains, Wistar Kyoto More Immobile (WMI) and Less Immobile (WLI), and their reciprocal female F1 offspring. The parental strains differ in depression-like behavior and substance use vulnerability, with WMI rats consuming more oxycodone than WLI controls. Voluntary consumption was measured with an operant licking self-administration protocol that delivered 60 l drug per reward. Across four experimental stages, oxycodone concentrations increased from 0.025 to 0.1 mg/ml, and session durations increased from 1 to 4 hours. Female offspring showed a parent-of-origin effect. F1 females sired by WMI fathers (WLIxWMI) displayed accelerated escalation during the transition from 1-hour to 4-hour sessions in Stage 2 and consumed more oxycodone than reciprocal WMIxWLI females across expanded-access stages. This vulnerability was associated with increased licking during the drug-unavailable timeout period. In WMI and reciprocal WMIxWLI female, consumption was regulated by the drugs subjective value, as measured by lick microstructure, during Stages 1 and 2. This relationship was absent in WLIxWMI females during Stage 2. Together, these findings suggest that paternal WMI lineage is associated with a rapid transition to high oxycodone intake and cue-directed drug seeking, and identify a parent-of-origin effect that may contribute to female vulnerability to addiction.
Dai, Y.; Seielstad, A. K. L.; Hinman, J. R.
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Social isolation has profound effects on behavior and cognition, but these effects can differ across sex and behavioral domains. We asked how social isolation shapes foraging decisions in male and female rats using a patch-leaving task that combines spatial navigation with sequential stay-or-go choices across varying travel costs and reward depletion rates. All groups scaled patch residence times with travel cost in a manner consistent with the marginal value theorem yet consistently overstayed beyond the optimal leaving time. The magnitude of overstaying was shaped by a strong interaction between sex and social status, with socially isolated females leaving patches closest to optimal and consuming food at the highest rate. Their foraging was accompanied by a coherent spatial and behavioral profile where the socially isolated females spent more time idle, preferentially occupying protected regions near the door and corridor, and avoiding the exposed patch center during both active foraging and periods of idling. These patterns are consistent with a conservative, safety-oriented strategy that simultaneously minimizes exposure and maximizes caloric return. Social isolation does not uniformly impair cognition but can selectively bias female rats toward efficiency-maximizing foraging decisions, consistent with the ecological pressures faced by outcast females in wild rat colonies.
Serda, A.; Canteloup, C.; Meunier, H.
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Inequity aversion, the sensitivity to inequitable outcomes or processes, has been widely studied in nonhuman primates since 2003. Yet, findings remain debated as some could be explained by alternative mechanisms such as frustration or loss aversion, so-called individual contrasts. Previous work on nonhuman animals has restricted the definition of inequity aversion to the social domain. Here, we propose distinguishing between two different forms: a socially driven form, which depends on comparison with another individual, and an individually based form, caused by a discrepancy between ones own effort and the expected outcome. Using a task-based methodology, we manipulated both effort and the amount of reward to test for the existence of those different forms and distinguish them from individual contrasts. We presented seven Tonkean macaques (Macaca tonkeana) and three brown capuchins (Sapajus apella) with low and high effort tasks associated with low and high reward quantities. To test for the presence of individually based inequity aversion, subjects were tested alone in an individual phase. In some of the trials, they were rewarded less than they deserved for the task. To test for socially based inequity aversion, two individuals performed the same task in a social phase but, in some trials, one received a higher-value reward than the other. We recorded the latency to engage in the task as an indicator of reluctance. In the individual phase, macaques were slower to engage with inequitably rewarded tasks, a pattern consistent with an individually based expectation of equity. By contrast, capuchins were faster in this context, suggesting that their responses were more likely driven by individual contrast effects. In a context of social inequity, both species slowed engagement in tasks with inequitable rewards, suggesting an aversion to socially based inequity. These results demonstrate that such a methodology provides a means to study non-social components of inequity aversion. Future studies, conducted on larger and more diverse samples, with rigorous motivational controls and explicit tests looking at the understanding of the link between task and reward, are needed to confirm whether nonhuman primates can display inequity aversion independently of social comparison.
Chernoff, C. S.; Hynes, T. J.; Avramidis, D. K.; Ramaiah, S.; Lee, A. C.; Khoshnevis, A.; Hrelja, K. M.; Winstanley, C. A.
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The locus coeruleus noradrenaline (LC-NA) system is a key regulator of arousal, attention, and reward learning. Noradrenaline plays a critical role in impulse control, and recent evidence indicates the importance of noradrenaline signaling in cost-benefit decision making once choice strategies are established. However, whether the LC causally shapes the acquisition of decision strategies, and how this contribution may differ across sexes, remains unclear. We addressed these questions by chemogenetically inhibiting catecholaminergic neurons within the LC of adult tyrosine-hydroxylase Cre (TH::Cre) rats (n=69; 35 females) throughout acquisition of the cued rat gambling task (crGT), a probabilistic decision making paradigm that incorporates salient audiovisual reward-paired cues and simultaneously measures motor impulsivity. LC inhibition accelerated the development of risky choice strategies early in training in both males and females, reflected by impaired adoption of the most advantageous option and increased preference for risky options. Trial-by-trial analyses reveal that LC inhibition promoted switches in choice strategy following safe wins, while reducing switches away from risky options after both wins and losses. LC inhibition therefore seemed to encourage the repetition of actions that resulted in more uncertain outcomes. LC inhibition also selectively enhanced motor impulsivity in females, particularly early in training. These results provide causal evidence that the LC system guides the formation of optimal decisional strategies, while exerting sex-specific control over impulsive action.