Behavioural Brain Research

Anxiety disorders are among the most common psychiatric illnesses, with a significantly higher prevalence in females than in males. The open field (OF) and the elevated plus maze (EPM) are the two assays used most often to model anxiety-like behavior in mice. It is usually assumed that they index a common underlying trait, yet few studies have investigated this in a large group of male and female mice using an advanced analytical approach. The goal of these studies was to determine sex differences in locomotor activity and anxiety-like behavior in the OF and the EPM, and to establish which behavioral parameters correlate between the tests. Adult male and female C57BL/6 mice (n = 61; 29 male, 32 female) were given a single 15 min session in the OF, analyzed as a whole and in three consecutive 5 min blocks, and a single 5 min EPM trial. Males and females did not differ on any OF measure over the cumulative 15-minute session. Locomotion and stereotypy declined over time with females habituating faster than males while center exploration did increase. In the EPM, females made more closed-arm entries than males while open-arm exploration was identical. Every significant correlation between the two tests involved an activity measure. All four pairs formed between OF and EPM activity parameters were significant whereas none of the six pairs formed between OF center parameters and EPM open-arm parameters were significant. Hierarchical clustering revealed the same structure, placing the activity measures of both tests in one cluster, the EPM open-arm measures in a second, and the two OF center measures in a third. The cross-test activity correlation was strongest during the initial five minutes of the OF and weakened as the session progressed. These studies indicate that the OF and EPM yield convergent measures of activity, but divergent measures of anxiety-like behavior.

It is estimated that approximately fifty percent of the population will encounter at least one traumatic event during their lifetime; however, only six percent develop Posttraumatic Stress Disorder (PTSD), a trauma-related disorder characterized by persistent alterations in affect and cognition, including an exaggerated fear response. It is well established that females (9.7%) are more than twice as likely as males (3.6%) to be diagnosed with PTSD. Nevertheless, a significant challenge remains in understanding how the severity of traumas experienced in childhood versus adulthood influences PTSD development across sexes. To address this challenge effectively, the adoption of preclinical animal models that accurately reflect these key characteristics is crucial. The Stress Enhanced Fear Learning (SEFL) paradigm in rodents encapsulates some of these complexities associated with PTSD, such as persistent fear sensitization following exposure to acute trauma. This study investigates how stress severity and developmental timing affect the long-term maintenance of SEFL in male and female rats. Juvenile and adult rats were initially subjected to no stress (control, context only), low stress (1 footshock), moderate stress (3 footshocks), or high stress (15 footshocks), followed by an extinction session either one day (recent) or sixty days (remote) later. Subsequently, to evaluate SEFL in a new context, all subjects received a single footshock and were tested the following day. Shortly after stress induction, all groups displayed SEFL. Although the effects persisted for sixty days in adult males and juvenile females, even at the lowest stress level, they were significantly reduced in juvenile males and adult females. These findings offer novel insights into sex-related differences in the persistence of SEFL and introduce new considerations regarding how the timing of developmental stressors influences future threat encoding and fear responses.

Intergroup conflict is one of the most significant issues in human society. In the 1950s, Sherif et al. reported that intergroup conflict could be artificially induced in boys through intergroup competition with tug-of-war and ball games. Since this iconic study, researchers have developed various experimental methods to replicate intergroup competition and/or conflicts. However, although intergroup conflicts in wild animals are often reported, it has been difficult to establish a situation of intergroup conflict in laboratory rodents that is discriminable from aggressive behavior individually. In this study, we established a novel experimental paradigm for intergroup competition in mice in which the members of each group shared objectives and tasks. Adult male ICR/Jcl mice were housed in groups of six, divided into two teams of three and repeatedly performed a competitive Tsunahiki task (tsunahiki means tug-of-war in Japanese). The competitive Tsunahiki task was conducted in an open field divided into two experimental fields, with three ropes stuck to a wall separating the fields. The mice were required to pull two ropes out faster than their opponent team to win, and only the winners could proceed to the reward area separated by a guillotine door. We demonstrated that the experience of the competitive Tsunahiki task induced attack bites selectively toward members of the other team (out-group members). Our findings suggest that intergroup competition induces intergroup conflict in mice, providing a technical breakthrough in elucidating the detailed neuroscientific mechanisms underlying intergroup conflict.

Background: ADHD is characterized by inattention and impulsivity. Stimulants such as amphetamine are the first line treatments for ADHD. Amphetamine (AMPH) works by increasing extracellular levels of dopamine and noradrenaline. Such stimulants are used to test predictive validity of animal tasks, where it has been reported that amphetamine improves rat 5-CSRTT accuracy when the session length is increased to 250 trials. This improvement in accuracy was observed later in the session as control performance declined. Proving that amphetamine can improve 5C-CPT task performance adds to the predictive validity of the task. No previous works has demonstrated the pro-attentional effects of amphetamine on sustained attention in rat 5C-CPT. We have previously shown that pharmacological manipulations of dopaminergic system improve waiting impulsivity in a rate dependent manner and the importance of analysing the data using Oldham method. The present study extends this work to investigate the effect of amphetamine on attentional processes. Objective: to investigate effects of amphetamine on attentional processes as measured by 5C-CPT task using correlational analysis and group performance. Methods: Trained female Lister hooded rats were tested with AMPH (0.1, 0.2 and 0.4 mg/kg) under reduced stimulus duration schedule (0.25,0.5,1,1.5 and 2s SD) over normal length session (120 trials). Correlational analysis (Oldham method) was used to understand the relationship between baseline performance measures and the change following administration of AMPH. Results: The highest dose of AMPH impaired attentional performance in the 5C-CPT under reduced SD challenge (0.5s,1s,1.5s and 2s). This impairment was due to increase in FAR. Previous studies in 5-CSRTT suggest that reducing the SD increases attentional demand in the form of reducing accuracy without affecting waiting impulsivity. However, the 5-CSRTT does not include non-target trials, therefore, it cannot be used to measure sustained attention (SI) and responsivity index. The 5C-CPT requires greater attentional resources than the 5-CSRTT.This study is the first to report that reducing the SD changes responsivity index (bias) rather than measures of sustained attention (sensitivity index) in the 5C-CPT. Control sensitivity index did not change until the SD was reduced to less than 0.5s and this change was due to a change in baseline responsivity index (bias). Performance under each reduced SD revealed that the highest dose of AMPH (0.4 mg/kg) showed a tendency toward reducing sensitivity index at 0.5, 1.0 and 1.5s SDs. Under 1.0s SD, the highest dose of AMPH changed sustained attention (SI, HR and FAR) and omission in a rate-dependent manner without changing responsivity index. Performance across the session revealed that the impairment in sustained attention was observed at the beginning of the session. In the third trial block, Oldham method revealed an inverse relationship between baseline accuracy and the change following administration of 0.2 mg/kg AMPH, indicative of a rate-dependent effect. Conclusions: This study successfully demonstrates rate-dependent effects of AMPH on measures of attentional performance in the 5C-CPT. This experiment also demonstrates that responsivity index is sensitive to reduced SD challenge. To our knowledge this is the first study to report the presence of a direct relationship between baseline sustained attention and magnitude of improvement following administration of 0.4 mg/kg AMPH and an inverse relationship between baseline accuracy and the change following administration of 0.2 mg/kg AMPH in 5C-CPT task. Future studies should test lower doses of amphetamine (0.05 and 0.1 mg/kg) over extended session length (250 trials) to reveal the pro-attentional effects of this drug on 5C-CPT performance measures.

Working memory has been considered a delay-dependent retention system, but variability in delay duration across species and tasks suggests that task-intrinsic factors may also contribute. Here, we investigated the effects of delay duration (75 s vs. 150 s) and task distance (0 m vs. 2 m) on working memory using a T-maze delayed alternation task with a movable home-cage apparatus in rats. At the 150-s delay, accuracy was 9% lower at 0 m than at 2 m (75% vs. 84%), with a similar numerical tendency observed at the 75-s delay (4% lower). A two-way repeated measures ANOVA revealed significant main effects of both task distance and delay duration, with no significant interaction (p = 0.217). Post hoc pairwise comparisons indicated that accuracy in the 0-m condition was significantly lower at 150 s than at 75 s (adjusted p = 0.038). At the 150-s delay, accuracy was also significantly lower in the 0-m condition than in the 2-m condition (adjusted p = 0.019). These results suggest that working memory retention is influenced not only by temporal constraints but also by task-intrinsic factors such as task distance, with the observed effects appearing independent and consistent with a two-factor framework.

RationalePsychedelic compounds such as psilocybin have attracted growing interest for their potential therapeutic effects in psychiatric disorders, with improvements in cognitive flexibility proposed as a possible mechanism of action. However, the effects of psychedelics on cognitive flexibility remain poorly understood. ObjectiveThis study aimed to examine the acute and post-acute effects of psilocybin (0.1, 0.3, 1 mg/kg) and lysergic acid diethylamide (LSD, (0.02, 0.04, 0.08 mg/kg) on cognitive flexibility in male rats. MethodsThis was tested using two variants of the probabilistic reversal learning task (PRLT): a touchscreen-based operant task and a more ethological foraging-based task. ResultsIn the touchscreen PRLT, acute psilocybin disrupted task engagement, with animals completing fewer trials and showing increased trial initiation latency, although psilocybin also showed a trend toward faster initial rule acquisition. However, psilocybin did not significantly alter the number of rule changes achieved, a canonical measure of cognitive flexibility, or feedback sensitivity. LSD similarly produced limited acute effects, although the highest dose reduced lose-shift probability, suggesting decreased sensitivity to negative feedback under some conditions. Post-acute effects of psilocybin were minimal in both PRLT variants and, where LSD effects were observed these occurred across different doses and timepoints without a consistent pattern. ConclusionsOverall, these findings suggest that serotonergic psychedelics do not robustly enhance reversal learning in these paradigms and that apparent learning effects may reflect transient disruptions in task engagement rather than improvements in cognitive flexibility. These results also highlight potential limitations of these PRLT paradigms for detecting psychedelic-induced changes in cognitive flexibility in rodents.

Fear conditioning studies have historically relied on freezing as the primary measure of conditioned fear despite evidence that defensive responding is behaviorally diverse and sexually dimorphic. The endogenous opioid system, particularly mu-opioid receptor (MOR) signaling, is known to regulate fear learning and conditioned analgesia, yet its role in alternative fear-related behaviors and sex differences remains unclear. Here, we investigated the effects of systemic naloxone administration prior to auditory fear conditioning on freezing, darting, shock responsivity, and ultrasonic vocalizations (USVs) in male and female rats. Adult Sprague Dawley rats received naloxone (5 mg/kg, i.p.) or saline prior to conditioning and underwent fear recall testing 24 hours later. Naloxone produced sex- and behavior-specific effects across conditioning and recall. During conditioning, naloxone increased freezing in males during baseline and early tone presentations, while females exhibited reduced shock-response velocity and increased post-shock freezing. Naloxone did not significantly alter darting or USV production during conditioning. During recall, freezing behavior did not differ across groups. Naloxone-treated females, however, exhibited a distinct alarm-calling pattern, with fewer callers overall but increased call output among those that vocalized. These findings suggest that MOR antagonism differentially alters distinct components of fear expression in a sex-dependent manner and support the idea that freezing and alarm calling may reflect separable aspects of fear processing.

Planaria exhibit remarkable regenerative ability, including the capacity to regrow complete heads and brains after decapitation. Here, we re-investigated whether regenerated planaria can preserve learned avoidance behavior, a phenomenon that has been reported previously but has been difficult to study due to unreliable experimental protocols. Using a light-to-food associative conditioning paradigm, planaria were trained to override their normal photophobic preference and then decapitated. Following a two-week regeneration period, behavioral responses to the conditioned stimulus were re-evaluated. Results indicated that the majority of regenerated planaria retained the learned response, supporting a model in which behavioral patterns can regenerate as well as anatomical patterns. By establishing a consistent, low-cost, and effective protocol for studying memory persistence through regeneration, such work may help inform future research on memory loss, resilience, and recovery in neurodegenerative diseases.

Animals differ in how they acquire and retain information, and modify their behavior while interacting with their environment. These differences have been linked to personality type, yet how personality type and sex influence reward-associated memory is not well understood. We investigated the effects of personality type, sex, days of conditioning, and food reward on learning and memory retention in zebrafish using the conditioned place preference paradigm. We conditioned zebrafish to associate a visual background with a food reward across eleven sessions and assessed memory recall seven days later by measuring duration, frequency of entry, and latency to first entry in the conditioned zone. We observed that bold fish had early conditioned zone engagement, whereas shy zebrafish gradually increased their behavior into the conditioned zone with repeated conditioning. With food reward, preference for the conditioned zone increased after 7 and 11 days post-conditioning relative to baseline. Seven days after the last conditioning with food reward, the preference for conditioned zone remained unchanged in shy fish. This suggests that shy fish retain the ability to recall the learned association for at least 7 days after conditioning. Overall, personality, food reward, and sex influence behavioral changes in food reward-associated cognition, with shy-treated males showing gradual increases in behavior into the conditioned zone. These findings suggest that personality and sex differences may depend on the nature and valence of the associative task to recall. Thus, this study emphasizes the importance of assessing memory retention alongside learning acquisition to understand the relationship between personality types and cognition.

Human interlocutors have strong expectations that guide when, how, and what is communicated, but the evolutionary origins of such normative expectations remain poorly understood. Vocal accommodation in marmosets, where individuals modify their calls to match partners, offers a potential model. Within an interactive closed-loop playback paradigm, marmosets experienced partner calls that either converged toward or diverged away from their own call structure. Marmosets responded affiliatively to convergence, whereas diverging calls elicited protest vocalizations. Importantly, the protests stopped when the calls converged again. Effects were partner-specific, indicating that marmosets expect bond partners, but not strangers, to converge during a conversation. Furthermore, individuals modified their calls to restore similarity to dissimilar partner playbacks. These findings identify marmoset vocal accommodation as a socially regulated behavior with normative properties.

Motivational deficit is a prevalent symptom across a wide range of neurodegenerative and neuropsychiatric disorders. Despite its clinical importance, first-line treatments for these disorders fail to effectively treat this symptom domain. In animal models, motivation is typically assessed in the context of extrinsic reward, where reward is delivered for completing an effortful action. However, many motivated behaviours occur in the absence of a tangible reward and are instead driven by intrinsic motivation. Previous work has shown that an extrinsic motivation task (effort for reward (EfR)) and an intrinsic motivation task (effort based forage (EBF) task) show opposing responses to a range of pharmacological manipulations. However, it is not clear whether intrinsic and extrinsic motivation dissociate in the context of endogenous behavioural variation. We therefore investigated whether these tasks were sensitive to behavioural variation across three different strains of mice (C57Bl/6JJRi, 129S2/SvPasOrlRj and BALB/cJRi) and whether strain profiles diverged across tasks. Here, we found that BALB/c mice showed the lowest levels of foraging in the EBF task, indicative of a low intrinsic motivational state but showed the highest levels of high effort responding in the EfR task, indicative of a high extrinsic motivational state. These differences were not driven by an anxiety-related phenotype and were therefore indicative of a motivation phenotype divergence across tasks. This work highlights the importance of moving away from considering motivation on a single axis, as findings can diverge depending on the nature of the motivational process. This has important implications for both phenotypic interpretation and the development of treatments targeting motivational dysfunction.

Budgerigars (Melopsittacus undulatus) are vocal-learning birds with well-developed auditory abilities, but how they behaviorally evaluate melodic and rhythmic structure in sound sequences remains unclear. We examined whether budgerigars show preferences for these acoustic features and whether such preferences differ between the sexes. Three male and three female budgerigars were presented with four 8-s sound sequences in a preference apparatus: Simple (no pitch or temporal variation), Melody (pitch variation only), Rhythm (temporal variation only), and Complex (both pitch and temporal variation). Preference was quantified as the time spent in the area associated with each stimulus. No statistically significant differences among the four stimuli were detected within individuals. However, effect-size estimates indicated that two females spent more time with sequences containing rhythmic structure, whereas males showed no consistent preference related to either melodic or rhythmic components. Multidimensional scaling further suggested greater separation among stimulus conditions in females than in males. Consistent with this pattern, condition differentiation indices were higher in all three females than in all three males, although the sex difference was not statistically significant. These results suggest a possible sex-related difference in how budgerigars behaviorally weight temporal structure, with females showing greater differentiation among auditory sequence types under the present testing conditions.

Theft, including shoplifting, extorts a pervasive societal and economic burden. However, the neurobehavioral mechanisms underlying recurrent theft remain sparsely understood. In this study, we investigated social cognition deficits in theft recidivists with kleptomania (TR+K) and instrumental theft recidivists without kleptomania (TR-K) compared to control subjects without criminal records (CT), for which the Social Norms Questionnaire (SNQ-22) to assess explicit moral knowledge, alongside the Dictator Game (DG) and Hawk-Dove Game (HDG) to evaluate discretionary and competitive resource allocation with others, respectively, were administered. Bayesian statistical analyses revealed that all groups demonstrated comparable social norm recognition in SNQ-22 and prosociality in the DG. However, distinct behavioral profiles emerged in specific contexts, such that TR+K exhibited more unfairness than CT and TR-K at discretionary resource allocations in the DG, whereas in the HDG, TR-K demonstrated more aggressive, resource-monopolizing responses, particularly when against an aggressive opponent, than CT and TR+K. These results suggest that theft recidivism may stem from contextual failures rather than general deficits in moral knowledge, which are distinct between TR+K rooted in the internal factor, such as heightened loss aversion, and TR-K characterized by impulsivity over the external factor, such as social conflicts with others.

ROR{gamma}t, encoded by Rorc, is a key transcriptional regulator of T helper 17 (Th17) cell differentiation, and IL-17A signaling has been implicated in neural development and behavior. We examined behavioral phenotypes in male ROR{gamma}t-transgenic mice with T-cell-biased ROR{gamma}t overexpression and their wild-type littermates. Mice were assessed using the resident-intruder paradigm and the light-dark box test, followed by body-weight measurement. ROR{gamma}t-transgenic mice had significantly lower body weight than wild-type mice. No genotype differences were detected in attack latency, attack frequency, light-compartment occupancy, light-dark transitions, or transition latency. In contrast, analysis of locomotor activity in 1-min bins revealed a significant genotype x time interaction. Transgenic mice showed nominally reduced locomotor activity during the first minute of the light-dark box test, although this single-bin comparison did not remain significant after correction for multiple comparisons. These findings indicate that T-cell-biased ROR{gamma}t overexpression is associated with altered temporal dynamics of locomotor activity in a novel environment rather than a generalized anxiety-like or aggression-related phenotype.

Japanese quail (Coturnix japonica) rely on an extensive vocal repertoire to coordinate social behaviour and respond to predation risk, yet how individual call types are modulated by predator identity remains poorly characterized. In this pilot case-series, two sexually mature Japanese quail (each contributing more than 2,000 classified vocalizations across repeated predator-exposure trials) were exposed to simulated aerial (hawk) and terrestrial (cat) predator stimuli across four social contexts, before, during, and after stimulus presentation. Vocalizations were classified, via blind dual-observer review, into 18 spectrographically distinct call types (an exploratory repertoire estimate, not independently statistically validated), of which 10 were acoustically characterized. Chi-square analyses of the full call-type composition revealed highly significant differences between hawk and cat exposure in both individuals (both p < 0.0001); call types 5 and 10 were significantly cat-biased and call type 2 was significantly hawk-biased in both individuals. An exploratory correlation suggested that call types with a higher maximum frequency tended to be relatively hawk-biased (Spearman rho = -0.67, p = 0.033, uncorrected for multiple comparisons). Independently, call-type composition shifted significantly between the pre- and post-exposure phases in all four individual-by-predator combinations (all p < 0.0001), driven substantially by a consistent post-exposure increase in call type 9 across both individuals and both predator classes. Additional exploratory analyses of social-context (mirror and concealed-conspecific) effects on call-type composition are presented in the supporting information. Given the small sample size (n = 2), these findings are presented as case-based, hypothesis-generating observations intended to justify and inform a fully powered follow-up study, rather than as population-level conclusions.

Background The head-twitch response (HTR) is a serotonin2A receptor (5-HT2AR) dependent behavioral correlate of serotonergic psychedelic action in rodent models. Although cortical 5-HT2ARs have been implicated in HTRs, the contribution of specific cortical circuits to this behavior remains poorly defined, with a few reports implicating the medial prefrontal cortex (mPFC) in the generation of HTRs. Results The serotonergic psychedelic, 2,5-dimethoxy-4-iodoamphetamine (DOI), induced head-twitch responses (HTRs) in male and female rats and mice, with sex differences noted only in mice. DOI also increased ear-scratch responses (ESRs), and reduced digging and grooming behaviors only in mice. While the DOI-evoked HTRs and ESRs were absent in 5-HT2AR knock-out (5-HT2AR KO) mice, reduced digging and grooming occurred in both wild-type and 5-HT2AR KO mice. We assessed the role of 5-HT2ARs in the mPFC in regulating DOI-induced HTRs using pharmacological and genetic approaches. Targeted DOI microinfusion into the mPFC did not induce HTRs in rats, in contrast to the robust increase in HTRs noted following systemic DOI administration. Local delivery of the selective 5-HT2AR antagonist, MDL100907, into the mPFC also had no effect on the systemic DOI-evoked increase in HTRs in rats. Experiments capitalizing on genetic strategies to perturb 5-HT2AR expression in the mPFC, indicated that viral restoration of 5-HT2AR expression in mPFC CaMKII-positive excitatory neurons was not sufficient to reinstate DOI-evoked HTRs or ESRs in 5-HT2AR KO mice. Further, conditional 5-HT2AR deletion in CaMKII-positive excitatory neurons in the mPFC did not alter systemic DOI-induced HTRs and ESRs in mice. Conclusions These findings indicate that the serotonergic psychedelic DOI induces species- and sex-specific behavioral effects in rodent models, with a robust 5-HT2AR dependence noted for DOI-evoked HTRs and ESRs. Further, we show that 5-HT2ARs in the mPFC do not appear to contribute to the enhanced HTRs and ESRs elicited by DOI.

Oxytocin (OT) and vasopressin (AVP) are neuropeptide hormones involved in regulating animal social behavior and a broad spectrum of physiological processes. Although their distributions are well documented in neuroendocrine regions of the forebrain and midbrain, their expression in the hindbrain remains poorly understood. Here, we used immunohistochemistry to quantify OT and AVP immunoreactive puncta within three auditory brainstem nuclei, the lateral superior olive (LSO), the medial superior olive (MSO), and the medial nucleus of the trapezoid body (MNTB) in six wild-caught rodent species differing in sociality. We also quantified the volume of these nuclei and examined variation in total brain volume across species and sociality. OT and AVP puncta count differed among species and social groups. Group-living species exhibited higher OT and AVP puncta counts than monogamous and solitary species in the LSO and MNTB. In the MSO, OT puncta counts did not differ among social groups, whereas AVP puncta counts were higher in group-living than in monogamous and solitary species. Total brain volume and the volumes of the MNTB and MSO differed among species, but not across social groups, whereas LSO volume did not differ among species or sociality. These findings revealed sociality-related variation in OT and AVP immunoreactive puncta within auditory brainstem circuits and suggest that neuropeptide signaling within early auditory brainstem pathways may contribute to the neural integration of social and auditory information.

The hippocampus is particularly vulnerable to hypoxia, yet freedivers, who repeatedly undergo voluntary breath-hold hypoxia, do not appear to show the memory impairments commonly reported after involuntary hypoxic exposure. We investigated whether freediving training is associated with functional connectivity reorganization at the whole-brain and hippocampal levels, and whether hippocampal connectivity relates to preserved episodic memory performance. Seventeen male recreational freedivers underwent fMRI before and after a 7-month standardized training period, and 20 matched aerobic-trained controls were assessed at baseline. Functional connectivity analyses examined (i) whole-brain ROI-to-ROI connectivity, (ii) seed-to-voxel connectivity from the bilateral hippocampus and selected cortical seeds, and (iii) associations between hippocampal connectivity and episodic memory. Compared with controls, freedivers showed distinct connectivity patterns during apnea and rest. After training, whole-brain analyses revealed reorganization involving salience, frontoparietal, sensorimotor, visual, and cerebellar systems. Hippocampal analyses showed reduced connectivity with sensorimotor and default mode regions, alongside increased connectivity with cerebellar and visual areas, with stronger effects after training. In freedivers, specific post-training hippocampal connectivity was associated with episodic memory performance. These findings suggest that repeated voluntary hypoxia during freediving training is associated with selective functional reorganization of hippocampal and large-scale brain networks. This pattern may reflect adaptive neuroplasticity linked to preserved episodic memory under intermittent hypoxic exposure.

Long-term opioid therapy is limited by analgesic tolerance and opioid-induced hyperalgesia, but the roles of genetic background, sex, and drug exposure remain unclear. We used 20 inbred strains from the Hybrid Rat Diversity Panel to examine thermal sensitivity, oxycodone analgesia, tolerance, and hyperalgesia-like changes following voluntary intravenous oxycodone or saline self-administration. Rats underwent tail-immersion testing before self-administration (Pre-SA) and after self-administration (Post-SA). Oxycodone analgesia was assessed using the percent maximum possible effect time course and the corresponding area under the curve. Pre-SA thermal sensitivity differed across strains and between sexes, and Pre-SA oxycodone analgesia also differed across strains. Oxycodone self-administration produced a sex-dependent increase in thermal sensitivity that was most evident in males. During Post-SA testing, oxycodone self-administering rats showed reduced analgesic responsiveness compared with saline controls, and the magnitude of this difference varied across strains. Within-strain Pre-SA-to-Post-SA comparisons identified tolerance-like reductions in several strains. Across strains and sexes, oxycodone self-administering rats showed a greater Pre-SA-to-Post-SA reduction in analgesic responsiveness than saline controls, consistent with analgesic tolerance. Total oxycodone intake was not associated with tolerance at either the strain-mean or individual-animal level. Heritability estimates were higher for thermal sensitivity and analgesia (H2 {approx} 0.28-0.40) than for changes in thermal sensitivity and tolerance (H2 {approx} 0.18-0.27). These findings demonstrate strain variation in thermal sensitivity and oxycodone analgesia, sex-dependent hyperalgesia-like effects, and reduced analgesic responsiveness following voluntary oxycodone intake.

PurposeSimilar vocal impairments occur in normative aging and Parkinsons disease (PD), making differential diagnosis challenging in early stages. The brains role in age and PD-related vocal dysfunction is unclear. This motivated our use of the zebra finch songbird model. We applied human acoustic analysis to evaluate aging and parkinsonian-like birdsong for shared and distinct features. MethodTwo open-access datasets of zebra finch song were analyzed using an expanded set of parameters that, in the case of humans, can detect subtle changes in voice. The aging dataset included younger, middle-aged, and older birds. The PD dataset included birds receiving viral injections into Area X to induce -synuclein overexpression or control treatment, recorded pre- and post-injection. Songs were automatically segmented into motifs using cross-correlation. Acoustic measures were extracted from harmonic, noisy, and mixed syllables. ResultsMiddle-aged birds differed from younger and older birds, showing non-linear trajectories in fundamental frequency measures and age-related increases in spectral slope, spectral emphasis, and intensity variability, whereas temporal parameters remained stable. In PD, pre-post changes occurred in both ASYN and controls, with ASYN birds exhibiting larger effects for fundamental frequency variability, decreasing frequency modulation, and vocal intensity measures. ConclusionsVocal aging in zebra finches was characterized by non-linear trajectories and prominent spectral and intensity-related changes. In a gene-driven PD state there were greater alterations in fundamental frequency variability and intensity regulation, features that may distinguish aging-from disease-related vocal variability. These findings further support the zebra finch as a translational model for vocal biomarker research.