Behavioural Brain Research

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.

Vocal communication depends not only on the acoustic features and rate of vocalizations, but also on their timing relative to the vocalizations of others. In this study, we examined whether ultrasonic vocalizations (USVs) produced by adult female Mongolian gerbils during freely moving social interactions are temporally related to the vocal timing of a partner. Using USVCAM, we assigned each USV to an individual caller and evaluated whether brief USVs exhibit turn-taking-like temporal organization by analyzing response latency after partner calls, call overlap rate, and circular-shift surrogate data. The offset-to-onset gaps of alternating vocalizations were concentrated within a short time range, with a median of 130 ms. In addition, the call overlap rate was significantly lower in the observed data than in the circularly shifted surrogate data, indicating that USVs occurred with short latencies after partner calls while being less likely to overlap with ongoing partner calls. Furthermore, USV counts were reduced in unoperated Ctrl animals that interacted with devocalized Mute animals. These findings suggest that gerbil USVs may be coordinated in relation to partner vocal timing and vocal input. This study provides a basis for understanding rodent USVs not merely as individual vocal outputs, but as temporally organized dyadic social signals.

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.

Post-Traumatic Stress Disorder (PTSD) commonly occurs alongside Traumatic Brain Injury (TBI), yet the chronic behavioral consequences of combined neurotrauma (i.e., PTSD and TBI) across the sexes remain unclear. Using a mouse model combining Single Prolonged Stress (SPS) as a model for PTSD and Controlled Cortical Impact (CCI) as a model for TBI, we assessed gait, anxiety-like behavior, and contextual fear learning and extinction at 2, 4, and 12-weeks post-injury. Combined neurotrauma produced early and persistent gait impairments in both sexes, delayed changes to anxiety-like behavior characterized by reduced avoidance of an anxiogenic environment, and long-lasting contextual fear recall deficits. Impaired learning was observed in males, where they demonstrated reduced fear acquisition and diminished extinction rates at later time points while females showed no deficits. Across testing and sex, peak deficits emerged at 4 weeks post-neurotrauma. Together, these findings define a sex- and time-dependent behavioral phenotype following combined neurotrauma and underscore the importance of modeling comorbidity to capture the temporal and neurobehavioral consequences of trauma exposure that more closely reflect clinical populations.

RationaleAdolescence is a period of heightened vulnerability to nicotine reinforcement. While zebrafish are a valuable model for investigating drug reward, standard conditioned place preference (CPP) assays typically test subjects in isolation. In this highly social species, solitary testing may act as an environmental stressor that confounds behavioral readouts. ObjectivesThis study examined how social context during testing (isolated vs. grouped) affects experimental attrition, behavioral stability, and nicotine CPP expression in late juvenile zebrafish. MethodsZebrafish housed in groups of four were tested either individually (isolated) or in their housing groups (grouped) during daily 20-minute sessions. Following baseline preference assessments, subjects underwent six days of conditioning pairing their initially non-preferred compartment with fish water or nicotine (0.5, 1.6, or 5.0 {micro}mol/L). Place preference, locomotion, and thigmotaxis were assessed on a drug-free test day. ResultsIsolated testing reduced distance traveled, decreased swimming speed, and increased time spent near tank walls, indicating heightened anxiety-like behavior. Experimental attrition was significantly higher in isolated (38.9%) than grouped (2.5%) subjects. Grouped subjects developed significant place preference at 1.6 and 5.0 {micro} mol/L nicotine, whereas preference was not detectable in isolated subjects. ConclusionsSolitary testing acts as a stressor that increases experimental attrition and masks place preference. Conversely, testing in the presence of conspecifics stabilizes behavior and facilitates the detection of nicotine reward in late juvenile zebrafish.

BackgroundTheta-frequency transcranial alternating current stimulation (tACS) over prefrontal cortex has been proposed to modulate working memory (WM), yet behavioral effects are often inconsistent. One potential source of variability is the tACS phase during stimulus presentation. ObjectiveWe tested whether behavioral performance during WM depends on the phase of prefrontal theta-tACS. MethodsTwenty participants completed two sessions of prefrontal 4 Hz tACS in a within-subject design, receiving active and sham stimulation in separate sessions. Participants performed a visuospatial change detection task (CDT) and a verbal N-back task. Stimulation effects on overall accuracy and reaction time were analyzed. Subsequently, phase-specific analyses related stimulation phase at task-relevant stimulus presentation to behavioral performance using circular regression models. Preferred phases across participants were tested using Rayleigh tests. ResultsNo significant overall effects of active compared with sham tACS on accuracy or reaction time were observed in either task. However, phase-specific analyses revealed stronger phase-dependent modulation of reaction time during active tACS compared with sham. In the CDT, this effect was present across difficulty levels, whereas in the N-back task it was observed only in the 3-back condition. No reliable phase-dependent effects were observed for accuracy. Preferred phases varied across participants and did not cluster around a common phase. ConclusionsPrefrontal theta-tACS can modulate WM performance in a phase-dependent manner even in the absence of average behavioral effects. The observation of phase-dependent reaction-time modulation across visuospatial and verbal WM tasks suggests that stimulation phase may be a relevant source of variability across cognitive domains.

Older adults are among the fastest growing groups of traumatic brain injury (TBI) patients and sustain disproportionately poor chronic outcomes. Despite this, the preclinical aging-TBI literature is limited. Beyond the limited presence of aging TBI studies, most studies published in this domain use moderate-to-severe, open head models of TBI, rather than closed head models of mild TBI (mTBI) and repetitive mTBI (rmTBI), the most clinically prevalent presentation. Whether age modulates the chronic behavioral consequences of rmTBI is unknown. In the current study, young (3-4 months) and aged (18-19 months) male C57BL/6 mice received either five mTBIs on alternating days to model rmTBI or sham procedures and underwent behavioral testing in the chronic phase for spatial memory and anxiety-related behavior. Because cross-age behavioral comparisons are confounded by age-related declines in activity and by large sample sizes necessary to detection interaction effects, we applied a three-tier analytical framework combining within-age comparisons, sham-normalized inter-age comparisons, and factorial two-way ANOVA. Contrary to our hypothesis that aging would worsen rmTBI behavioral deficits, age produced domain-divergent effects. Spatial memory deficits were directionally consistent in both young and aged mice but was attenuated in the aged group. Conversely, anxiety-related behavior emerged selectively in the aged mice showing increased thigmotaxis. Locomotion was driven by age alone, with no injury effect, confirming that the aged anxiety signal was not a locomotor artifact. A post-hoc sensitivity analysis indicated that resolving the Age x Injury interaction effect would require at least 44 animals per group. These findings show that age shapes the affective, but not the cognitive, consequences of chronic rmTBI, and underscoring that statistical strategy is inseparable from design in factorial injury studies.

Optimising the currently heterogenous efficacy of transcranial direct current stimulation (tDCS) interventions for motor learning requires identifying stimulation parameters facilitating performance while accounting for age-related differences in baseline performance and mechanisms underlying neuroplasticity. We systematically explored anodal tDCS intensity effects on implicit motor sequence learning (IMSL) in young and older adults. The study utilised a randomised, double-blind, counterbalanced crossover design. Ninety-six healthy participants (48 young adults, 48 older adults) completed a serial reaction time task (SRTT) with online sham or anodal tDCS over M1 at intensities of 1, 2, and 3 mA. The next day, memory consolidation was assessed in a recall test. Both age groups demonstrated IMSL and consolidation across conditions. While 1 mA tDCS improved IMSL in young adults by reducing reaction times, higher intensities had no significant benefit compared to sham. In older adults, anodal tDCS did not affect general task performance compared to sham, but 1mA tDCS acutely impaired selective sequence learning. The results demonstrate age-dependent and non-linear dose-dependent effects of anodal tDCS on IMSL. This underscores the necessity for age-adapted protocols for experimental and clinical tDCS applications. Future research should explore neurophysiological reasons for reduced tDCS efficacy in older adults found in the present study.

Non-human primates are crucial animal models in biomedical research including neurosciences. Legal frameworks ensure that participation of monkeys in biomedical research follows an ethical assessment, driven by specific guidelines for ensuring animal well-being. Those guidelines promote continued refinement of practices to improve animal wellbeing, yet quantitative data to inform such refinements is limited. In this context, we investigated the impact of modifications to the housing that created either navigational complexity or visual access to neighbouring animals on the behaviour of rhesus macaques. Then we quantified the value of different enrichment programmes based on manipulable objects. We showed that making navigation within a modular housing more complex, or adding transparent separations between housing units is associated with significant reduction of severe aggression, stereotypical behaviours and a significant increase of appeasing behaviours. We also observed a positive effect of manipulable objects with an increase in the expression of appeasing behaviours and a decrease in abnormal or stereotypical behaviours. Finally, our study revealed significant inter-individual variability that was not explained by sex, age, social network size or social status. Overall, our results point to the importance and benefits of environmental changes and enrichment protocols, and of the critical need for personalised enrichment programmes.

Octodon degus are long-lived, diurnal, and highly social rodents increasingly used in studies of aging and neurodegeneration. However, behavioral profiles of aged laboratory-housed degus remain incompletely characterized, limiting the interpretation of aging-associated functional and molecular phenotypes in this species. Here, we evaluated age-associated changes in locomotor activity, open-field exploration, social novelty behavior, and manually scored ethological responses in young and old degus maintained under long-term laboratory housing conditions. Automated behavioral tracking was performed during open-field testing and three-chamber social behavior testing. During open-field testing, old degus showed increased locomotor activity compared with young animals, including greater total distance moved, higher mean velocity, increased moving frequency, and longer cumulative movement duration. Old degus also showed increased center-zone duration and reduced thigmotaxis score. Manual ethological scoring revealed increased rearing and fecal boli in old animals during open-field exposure. In the three-chamber social behavior assay, young degus showed higher investigation frequency toward the novel intruder than toward the familiar cagemate, whereas old degus showed a lower social novelty discrimination index compared with young animals. Sex-stratified analyses did not identify significant male-female differences within young or old groups for the major open-field or social novelty metrics examined. Together, these findings indicate that aging in laboratory-housed degus is associated with a mixed behavioral profile involving increased stress-related ethological responses and reduced social novelty preference reminiscent of dementia-like behavioral changes observed in Alzheimers disease. This behavioral framework provides a practical reference for future studies examining behavioral heterogeneity and molecular correlates of brain aging in degus. Lay SummaryOctodon degus are long-lived, highly social rodents that are increasingly used to study aging and age-related neurodegenerative disorders. However, interpreting behavioral changes in aged degus requires a clear understanding of how aging affects activity, exploration, social behavior, and stress-related responses under laboratory housing conditions. In this study, we compared young and old degus using open-field testing, three-chamber social behavior testing, automated video tracking, and manual scoring of selected behaviors. Aged degus did not show a simple reduction in behavioral activity. Instead, they showed increased movement during behavioral testing, increased rearing behavior, greater exploration of the center of the open-field arena, and increased fecal output during open-field exposure. These findings suggest that aged degus show increased exploratory activity together with altered stress-related responses in a novel environment. Aged degus also showed reduced preference for investigating a novel social partner, consistent with a dementia-like cognitive impairment. Together, these results define a behavioral profile of aged laboratory-housed degus and provide a practical reference for future studies using this species to investigate aging, social behavior, and neurodegeneration-related phenotypes.

ObjectiveAging is associated with changes in cortical excitability and altered responsiveness to benzodiazepines, but the effects of benzodiazepine challenge on motor cortical paired-pulse physiology in older adults remain incompletely understood. We examined whether intravenous midazolam differentially modulates corticospinal excitability and short-interval paired-pulse transcranial magnetic stimulation (TMS) responses in younger and older adults. MethodsFifteen younger adults (18-35 years) and fifteen older adults (50-69 years) underwent single-pulse and paired-pulse TMS of the left primary motor cortex at baseline and during intravenous midazolam administration. Single-pulse motor evoked potential (MEP) amplitude was used to assess corticospinal excitability. Short-interval paired-pulse responses were quantified as the ratio of conditioned to unconditioned MEP amplitude. ResultsAt baseline, younger adults showed greater corticospinal excitability than older adults, reflected by larger single-pulse MEP amplitudes (adjusted p = 0.04). Younger adults demonstrated paired-pulse inhibition at baseline, reflected by a conditioned/unconditioned MEP ratio below 1.0 (ratio = 0.73; adjusted p < 0.01), whereas older adults did not show inhibition and instead had a mean ratio above 1.0 (ratio = 1.25). Midazolam reduced single-pulse MEP amplitudes in both groups. During midazolam administration, paired-pulse inhibition was no longer observed in younger adults, and older adults continued to show no evidence of inhibition. ConclusionsYounger and older adults differed in baseline corticospinal excitability and in short-interval paired-pulse TMS responses. Intravenous midazolam reduced corticospinal excitability and altered paired-pulse response patterns, eliminating baseline paired-pulse inhibition in younger adults while producing little measurable change in older adults. These findings suggest that aging may modify the net motor cortical response to benzodiazepine challenge. The results should be interpreted in relation to the paired-pulse stimulation parameters used and support further studies using complementary approaches to characterize age-related differences in inhibitory and facilitatory motor cortical circuits.

Abstract Objectives To evaluate and compare the neuro-behavioural safety profiles of piroxicam and nitroglycerine by investigating their differential effects on cognitive function, spatial and recognition memory, and hippocampal neurochemistry in a di-oestrous female Wistar rat model. Methods Female Wistar rats at di-oestrous were randomly assigned to receive distilled water, piroxicam, or nitroglycerine orally for four consecutive days. Following treatment, spatial and recognition memory were evaluated using standard behavioural paradigms. Hippocampal tissues were analysed for acetylcholinesterase and glutamate activity, oxidative stress markers, and neuroinflammatory indices. Results Piroxicam improved recognition memory and was associated with increased glutamatergic activity and a compensatory rise in superoxide dismutase. However, it also elicited elevated nitric oxide signaling, lipid peroxidation, and localized neuroinflammatory markers in the hippocampus. In contrast, nitroglycerine impaired non-spatial memory during di-oestrous. Although both treatments preserved working memory, they produced distinct effects on object recognition, memory discrimination, oxidative stress parameters, and neuroinflammatory mediators. Conclusions Piroxicam and nitroglycerine exert differential effects on cognition and hippocampal neurochemistry during di-oestrous. Piroxicam improved recognition memory and produced distinct hippocampal neurochemical alterations, whereas nitroglycerine impaired recognition memory. These findings highlight the influence of menstrual pain therapeutics on cognitive function and hippocampal physiology under hormonally sensitive conditions. Keywords: cognitive function; cognitive impairment; cyclooxygenase inhibitors; neuroinflammation; neurochemistry

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.

Many perceptual skills improve with a few days of training. However, weeks or months of practice may be required to reach a level of expertise on complex tasks (Watson, 1980). Here, we explored how gerbils attain expertise on a difficult task: amplitude modulation (AM) rate discrimination at very shallow AM depths, similar to the depths used during vocal communication. Using an appetitive Go-Nogo procedure, we first trained 6 gerbils to perform an AM discrimination task (Nogo: 4 Hz; Go: 4.25-10 Hz) at a depth of 0 dB (re: 100% depth). Animals were then trained to perform AM discrimination at successively shallower depths, from -3 to -18 dB, requiring an average of 5-10 days of practice to reach a performance metric of d[&ge;]1 for each depth. Finally, we determined that AM discrimination thresholds were nearly identical between 0 to -12 dB, and only slightly elevated at -15 dB. Improvements in performance were accompanied by a large reduction in response time during procedural learning, and a gradual reduction of response time during perceptual learning, even as AM depth became shallower (i.e., more difficult). The shallowest depth at which gerbils displayed peak performance on the AM discrimination task is similar to their lowest AM depth detection thresholds. These results suggest performance on challenging auditory perceptual tasks require prolonged practice, and is accompanied by increased automaticity (i.e., lower response time) that stabilizes once expertise is achieved.

Healthy young and older adults completed two randomized sessions of split-belt treadmill walking, with and without a concurrent cognitive task. When the single-task session occurred first, both age groups showed savings in step length asymmetry during re-adaptation one week later. However, performing the dual-task session first reduced savings, and this order-effect was greater in older adults compared to young adults. These findings suggest that cognitive load during initial motor adaptation interferes with savings, but once stored, locomotor readaptation is resilient to dual-tasking.

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.

Memory impairment is a common and sometimes overlooked feature of major depressive disorder, and cognitive deficits may precede the onset of depressive symptoms in some cases. However, the cognitive benefits of first-line treatments such as SSRIs are mixed. Tianeptine is an atypical antidepressant and cognitive enhancer that neither interacts with monoamine receptors nor inhibits the reuptake of their neurotransmitters. Its antidepressant efficacy in animal models requires activation of the mu-opioid receptor (mu-OR) and phosphorylation of the AMPA receptor. However, the receptors that mediate its memory enhancing actions have never been investigated. We therefore tested the ability of tianeptine to improve spatial memory in a cross-maze task in wild-type (WT) mice compared to its effects in mice with global knockout of either the mu-OR or delta-OR. In parallel, we assessed the effects of tianeptine on hippocampal oscillatory activity and spontaneous locomotion in the same genotypes. Adult male and female WT, mu -/-, and delta -/- mice on a C57BL/6J background were implanted with hippocampal electrodes for the recording of local field potential (LFP) oscillations. Consistent with our previous observations in anaesthetised rats, injection of tianeptine (10 mg/kg and 30 mg/kg SC) caused a dose-dependent increase in beta-frequency power in WT mice that was maximal at circa 25 Hz. The same effect was observed in delta -/- mice, but the increase in beta was completely absent in mu -/- animals. As others have reported previously, tianeptine also caused a mu-OR-dependent increase in spontaneous locomotor activity, but with a time-course that was distinct from the increase in beta power. Separate groups of WT, mu -/-, and delta -/- mice were tested for their ability to learn a food-rewarded spatial memory task in a cross-maze. Over a 20-day training period, sub-groups of each genotype received either tianeptine (10 mg/kg SC) or vehicle injection 30 min before testing. Tianeptine increased the percentage of correct trials and the number of allocentric (place) responses in WT mice, but did not enhance memory in either mu -/- or delta -/- mice, even though both genotypes were able to learn the task. These results indicate that the ability of tianeptine to drive hippocampal beta oscillations is dependent on the mu-OR, whereas its memory-enhancing actions require the presence of both mu- and delta-ORs. The latter result is consistent with the actions of tianeptine on postsynaptic AMPA receptors, and we are currently exploring the signalling pathways involved in this process.

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.

It is becoming increasingly clear that chronic exposure to lower levels of ethanol impact learning and behavior. To determine the impact of chronic low-dose ethanol exposure on sensitivity to changes in stimulus value, a conditioned taste aversion procedure was used. Adult male and female mice underwent a sucrose two bottle-choice drinking paradigm. Each day, mice received an injection of either low-dose ethanol (0.5g/kg) or saline two hours after sucrose access for 20 days. This was followed by a lithium chloride (LiCl)-induced conditioned taste aversion (CTA) paradigm in which 0.15M LiCl or vehicle injection was administered immediately after sucrose consumption for three days. On the fourth day, changes in sucrose consumption were analyzed. Chronic exposure to low-dose ethanol did not affect sucrose consumption in either female of male mice during two-bottle choice. In female mice, a history of chronic low-dose ethanol exposure blocked the development of LiCl-induced CTA. A history of chronic low-dose ethanol did not impact LiCl-induced CTA in male mice as both ethanol-naive and -exposed male mice who underwent LiCl pairing reduced sucrose consumption. This suggests that low-dose ethanol alters aversion-related learning in female mice which may have implication for development of aberrant behavior and risk for alcohol use disorder (AUD).

In nature, the most common drivers of lethal aggression are predation and territorial defense. In northeastern Poland, the yellow-necked mouse (Apodemus flavicollis) coexists with several rodent species, including the bank vole (Clethrionomys glareolus). Compared to voles, A. flavicollis is larger, physically stronger, more aggressive, and dominant in the social ecosystem. However, no visually documented instance of a lethal attack by this species has been reported up to date. Here, we present the first recorded case of a fatal attack by a yellow-necked mouse following an encounter with a bank vole. A near-lethal attack is also reported. Importantly, these attacks were not predatory, as no consumption occurred. The attacks appeared instead to be related to interspecies competition, i.e., to competitive interactions between two species that live in the same habitat and use the same type of resources. Notably, while the aggressiveness of yellow-necked mice towards bank voles was known, it was unknown that it could take such extreme forms. Since, in rodents, most competition-related agonistic interactions are aimed at distancing the competitor, the physical destruction of the competitor appears as a surprisingly extreme way of addressing the game of interspecies competition through definitive removal of the opponent. Our observations highlight the need for further research on interspecific aggression among small mammals. They also emphasize the importance of field-based methods, such as camera trapping and continuous video monitoring, which allow for direct observation of animal behavior in natural settings and can reveal rare or previously overlooked interactions.