Traumatic brain injuries (TBIs) result from impact to or rapid displacement of the brain and can lead to various neurological deficits involving working memory, decision making, and anxiety. While large-scale effects of brain damage are well-described for more severe TBIs, less is known about the extent and duration of cognitive deficits at the mild level. Interval timing can provide a helpful window into cognition in mice and humans. Interval-timing behavior is impaired in a wide range of neuropsychiatric disease states, but less is known about whether it is impaired by mild TBI (mTBI). Furthermore, novel object recognition and the Barnes maze tests are valuable assays for evaluating spatial learning, working memory, and anxietylike behavior in mice. Here, we employed a weight-drop model of mTBI to investigate cognitive and behavioral changes resulting from mTBI treatment. mTBI mice were not consistently impaired in either interval timing or novel object recognition, but they demonstrated impaired spatial memory in the Barnes maze. Interestingly, between-sex comparisons revealed impairments in male mTBI mice in the interval-timing task, suggesting that male and female mice may be differently affected by mTBIs. (PsycInfo Database Record (c) 2026 APA, all rights reserved).
Many of the brain's functional regions display lateralization, meaning they are more specialized to one hemisphere than the other. The visual word form area (VWFA) is one such region; its specialization for written scripts, which develops only after literacy, is consistently dominant on the left in adults. The experience-dependent nature of the VWFA makes it a prime opportunity to investigate the development of functional laterality in the human brain. Therefore, we ask, "What neural correlates relate to the development of word laterality in children?" We tested two potential sources of this word laterality: (a) structural connectivity (s-connectivity) of the VWFA with the high-level language network in frontal and temporal cortices and (b) activation in these language regions. To do so, we scanned reading children (4-13 years) on a visual functional magnetic resonance imaging localizer to define the VWFA and its word selectivity and a separate auditory functional magnetic resonance imaging localizer to define language regions and their linguistic selectivity, and we collected diffusion-weighted imaging to examine white matter connectivity. Probabilistic tractography was used to quantify white matter connections between our subject-specific functional regions. VWFA word laterality was predicted by the positive interaction between laterality of s-connectivity to temporal language regions and laterality of temporal language regions' selectivity, suggesting that the VWFA tends to be more left-lateralized when both temporal language areas are left-lateralized and the VWFA has strong s-connectivity to that left-lateralized language network. More generally, our findings suggest that both s-connectivity to related regions and activation patterns in those connected regions may play a role in the development of functional laterality, and shed light on the development of the neural circuitry that underlies reading. (PsycInfo Database Record (c) 2026 APA, all rights reserved).
Excessive aggression induced by social isolation (SI) has been closely linked to dysfunction in prefrontal circuits, particularly the anterior cingulate cortex (ACC). Topiramate, an antiepileptic drug known to enhance GABAergic and inhibit glutamatergic transmission, has demonstrated antiaggressive effects. In our previous work, we showed that topiramate's antiaggressive effects were associated with reduced neuronal death, improved neuronal morphology, and attenuated neuroinflammation in the ACC following SI. However, its impact on ACC neuronal activity remains poorly understood. In this study, we investigated the effects of topiramate on the spontaneous activity of ACC neurons in a mouse model of SI-induced aggression. Additionally, we explored whether direct restoration of ACC activity via high-frequency stimulation could similarly reduce excessive aggression. Systemic administration of topiramate (30 mg/kg, intraperitoneally) significantly increased attack latency, reduced attack frequency, and enhanced sociability. In vivo extracellular recording of spontaneous activity revealed a 50% reduction in ACC firing in isolated mice, which was partially restored (∼30%) by topiramate treatment. Moreover, high-frequency stimulation applied to the ACC markedly decreased aggressive behavior and robustly promoted social interaction. Together, these results provide convergent behavioral and electrophysiological evidence that SI-induced aggression is associated with ACC hypoactivity. The finding that both topiramate treatment and high-frequency stimulation of the ACC effectively reversed these deficits highlights the ACC as a key target for therapeutic interventions to treat aggression-related neuropsychiatric conditions. (PsycInfo Database Record (c) 2026 APA, all rights reserved).
Gait speed has been associated with executive function in aging. To date, few studies have examined multiple mobility measures in parallel across the adult lifespan. Understanding how distinct aspects of mobility are associated with executive function may clarify modifiable behavioral targets to promote healthy aging. Community-dwelling adults (N = 223, Mage [SD] = 52.7 years [17.5], range = 18-85 years; 135 females) from the Fitness, Aging, Stress, and Traumatic Brain Injury Exposure Repository completed mobility and cognitive testing. Spatiotemporal gait and static balance were assessed using LEGSys and BalanSens accelerometer sensors. A composite measure of executive function was derived from subtests of the Wechsler Adult Intelligence Scale-IV (Digit Span backward, sequencing) and Delis-Kaplan Executive Function System (Trail Making Test-number-letter switching, color-word interference-inhibition, inhibition switching). Relative importance analyses explored contributions of mobility measures to executive function in relatively older adults (55+ years) and relatively younger adults (18-54 years). Hierarchical linear regressions examined mobility-executive function associations in each age group. Static balance contributed to executive function in both groups, whereas gait cycle measures explained variance in executive function among older adults. Among older adults, stride velocity (β = 0.13, p = .028) and cadence (β = 0.12, p = .048) explained an additional 3.4% and 2.8% of variance in executive function beyond age and education. No associations were observed among younger adults. Mobility and cognition relationships may differ across adulthood. In older adulthood, cadence emerged as a distinct mobility marker of executive function beyond gait speed, underscoring distinct features of gait as potential modifiable lifestyle variables important for healthy aging. (PsycInfo Database Record (c) 2026 APA, all rights reserved).
Previous research has demonstrated changes in neural oscillations associated with varying levels of roughness during active-touch exploration of surfaces. In the present study, we aimed to investigate changes in neural oscillatory activity and softness perception during touch exploration of skin. Two experiments were conducted. Study 1 evaluated active touch of artificial skin samples mounted to a purpose-built touch sensor, whereas Study 2 investigated active stroking of one's own forearm. In both experiments, the substrates were treated with commercially available bar soaps to deliver either a soft or draggy skin feel. Oscillatory brain activity was measured using a 129-channel electroencephalography system. In 31 participants, changes in oscillatory band power were evaluated in relevant frequency bands during touch exploration periods. For the artificial skin study, the soft condition led to lower alpha-band power over bilateral somatosensory cortices, which has previously been proposed as a marker of reduced roughness, compared to the draggy condition. Similar results were obtained during the self-touch paradigm, which additionally led to reduced theta-band changes over the frontal and central-parietal electrodes indicating modulation of activity involved in affective (pleasant) touch. Using a novel and highly controlled experimental approach using a novel artificial skin paradigm and active exploration during self-touch of participants own skin, we were able to demonstrate for the first time the neural correlates associated with softness perception of skin and their impact on brain activity associated with affective touch, thereby advancing our understanding of brain oscillatory activity during active-touch exploration of skin. (PsycInfo Database Record (c) 2026 APA, all rights reserved).
Normal explicit/declarative memory requires a system of anatomically related structures in the medial temporal lobe that includes the hippocampus and the entorhinal, perirhinal, and parahippocampal cortex. Although extensive medial temporal lobe damage in primates causes robust anterograde amnesia, defining the contribution of the hippocampus proper has proved challenging. We revisited that enduring puzzle here, directly addressing a number of factors suspected to contribute to conflicting results across earlier studies. Among them, we explored the effects of selective hippocampus lesions produced by two common excitotoxin methods, ibotenic acid and N-methyl-D-aspartic acid. Sample sizes were substantial, and all behavioral testing was conducted postoperatively. Performance was assessed on several standard procedures designed for monkeys, including multiple variants of the delayed nonmatching-to-sample test of visual object recognition, a series of rapidly acquired two-choice object discriminations, and a delayed response test of spatiotemporal memory. We used task-specific parametric manipulations (e.g., increasing retention intervals and reduced stimulus set size) to systematically vary demands on memory and test/retest analyses to enhance sensitivity for detecting impairment. Although both lesion groups sustained substantial hippocampal damage, their performance failed to differ from that of intact controls on any task, under any key test condition, regardless of data analytic strategy. The findings constrain plausible accounts of extant discrepancies in the literature and, moreover, highlight the need for fresh perspectives on the core operating characteristics of memory mediated by the primate hippocampus. (PsycInfo Database Record (c) 2026 APA, all rights reserved).
Aging is associated with decline in spatial learning, cognitive flexibility, and working memory, yet the extent to which biological sex modulates changes in cognitive function remains unresolved. While sex differences are evident in pathological brain aging, sparse insights from healthy aging populations suggest that sex effects on cognition are modest and domain specific. To systematically test effects of biological sex across the lifespan on specific aspects of cognitive function, we examined age- and sex-related changes in spatial cognition in a large cohort of Fischer 344 rats (N = 373), including young (4-8 months), middle-aged (12-16 months), and older aged (22-26 months) males and females. Rats were assessed on spatial reference learning, reversal learning, and working memory versions of the Morris water maze, with performance quantified using proximity-based measures, providing sensitive, individualized indices of spatial learning. Across all tasks, age accounted for the largest proportion of variance, with older rats exhibiting impairments in spatial learning, flexibility, and working memory relative to young adults. In contrast, effects of sex or interactions with age were limited to certain aspects of performance and were substantially smaller relative to age and training effects. Specifically, a female-specific association between spatial reference memory and reversal learning was observed despite comparable overall performance. Performance on visible-platform control trials did not indicate gross sensorimotor impairments that would account for age-related spatial deficits. Together, findings demonstrate age is the primary determinant of spatial cognitive decline under normative conditions, while sex-related influences, if present, are subtle and task dependent. (PsycInfo Database Record (c) 2026 APA, all rights reserved).
The hippocampus plays a critical role in contextual learning and memory processes. The ability to associate memories and behaviors with the learning context likely involves interactions between the hippocampus and other brain regions where the basic elements of the memory may be encoded. Here, we examined interactions of the hippocampus and the olfactory system using a contextually cued conditional discrimination task that required rats to remember that one odor from a pair of odor cues is rewarded in one context, but the opposite odor is rewarded in a different context. We used muscimol to inactivate the anterior olfactory nucleus, a key target for hippocampal output to the olfactory system, and the ventral hippocampus. We also performed crossed-hemisphere inactivation of the anterior olfactory nucleus in one hemisphere and the hippocampus in the other. All three inactivation procedures severely impaired performance. These results indicate that interactions between the hippocampus and anterior olfactory nucleus are critical for context-dependent odor memory. (PsycInfo Database Record (c) 2026 APA, all rights reserved).
Fear, an adaptive response to danger situation, is vital for the survival of both human beings and rodents. Predator odor-related cues and contextual fear work as valuable models for studying neurobiological circuits, providing insights into unconditioned and conditioned fear-related behavioral and physiological responses, including fear-related antinociception. This study investigated whether a fear paradigm based on predator odor cues could trigger the defensive antinociceptive phenomenon. Our findings indicate that while both the exposure to different predator odor cues and the re-exposure to the experimental context elicit similar defensive behaviors, such as the head-out response (an inhibitory avoidance behavior), only the exposure to the predator odor cues induced defensive antinociception. Notably, during the re-exposure to the experimental context, the endogenous pain modulatory system is not recruited, suggesting that defensive antinociception is not universally elicited by all fear-related reactions. Instead, defensive antinociception appears to be modulated by distinct neural circuits and olfactory perception-dependent mechanisms that adjust dynamically according to threat imminence. Thus, antinociception emerges as part of the immediate defensive response to a threatening odor cue, rather than as a consequence of fear memory retrieval. (PsycInfo Database Record (c) 2026 APA, all rights reserved).
Associating a taste with a positive or negative consequence is a robust form of learning that benefits survival by shaping future taste decisions. A robust example is conditioned taste aversion (CTA), wherein tastes associated with malaise are later avoided (Garcia et al., 1955; Lubow, 2009; Reilly & Bornovalova, 2005; Reilly & Schachtman, 2009). One factor that can modulate the strength of CTA learning is previous exposure to the conditioned taste. For example, familiarity with a taste weakens future learning toward that taste (Lubow, 1973, 2009; Lubow & Moore, 1959), demonstrating that even mere exposures to taste impact future plasticity. Taste exposure is ubiquitous in everyday life and begins in-utero. Recently, research has suggested that experience during specific periods of early life development can also induce preference and familiarity toward stimuli later in life, thus it is important to understand whether experience with tastes have differential effects on learning across the lifetime. Here, we explore for the first time whether sucrose exposure during different developmental stages in Long Evans rats (N = 55) differentially impacts sucrose-CTA learning in adulthood. Such an effect would suggest the existence of unique plasticity mechanisms that are influenced by taste exposure across different development phases. Interestingly, we report an enhancement of aversion learning in adult rats who were exposed to sucrose through their mother, either during gestation or lactation. These findings suggest that taste exposure during specific phases of early development holds unique significance for neuroplasticity and learning in adulthood. (PsycInfo Database Record (c) 2026 APA, all rights reserved).
Studies of brain lesions or volumes indicate that the integrity of medial and lateral temporal lobe structures is important for news event memory accuracy, but the relationship between cortical thickness and news event memory accuracy has not yet been investigated in older adults. In a mixed sample of 70 older adults with variable cognitive abilities but without dementia, we investigated the relationship between cortical volume, hippocampal volume, and cortical thickness with news event recognition memory accuracy across the entire adult lifespan using the Retrograde Memory News Events Test. Partial Least Squares analysis was used to identify brain regions where news event memory accuracy scores significantly correlated with cortical volume, hippocampal volume, and cortical thickness. We found that mean news event memory accuracy significantly correlated with volume/thickness for a network of regions that included the hippocampus, medial/lateral temporal lobe, medial/lateral parietal lobe, and specific areas within the medial/lateral prefrontal cortex. Poorer performance was associated with a thinner cortex (and smaller volumes). Almost all regions in this network exhibited decreasing brain-behavior correlations as the age of memory increased; thus, retrieval of remote memories was less reliant on the network. We also found regions in this network that were not identified by the Retrograde Memory News Events Test posttest (a measure of episodic anterograde memory for the Retrograde Memory News Events Test content) nor traditional neuropsychological tests. The regions identified as uniquely contributing to news event memory overlap with regions known to exhibit increasing Alzheimer's disease pathology and cortical thinning when pathology begins to spread outside of the medial temporal lobe. (PsycInfo Database Record (c) 2026 APA, all rights reserved).
Cocaine's reinforcing properties are a key factor underlying the broad prevalence of cocaine use disorder. Few behavioral measures are capable of assessing cocaine-induced euphoria in murine models, limiting effective treatment options. However, positive affective states can be measured in rats by assessing the production of high-frequency, 50-kHz, vocalizations. Oxytocin (OXT) has been shown to attenuate cocaine-mediated behaviors in rodent models; however, the effect of OXT on cocaine-induced euphoria remains unknown. We addressed this by randomly assigning female rats to saline-saline, saline-cocaine, OXT-saline, or OXT-cocaine conditions and then assessing ultrasonic vocalizations. We found that saline-cocaine animals emitted a significantly higher percentage of 50-kHz calls relative to the other conditions, indicative of cocaine's euphoric effects. Notably, an OXT pretreatment prevented the cocaine-induced increase in high-affect calls. We also found that OXT significantly increased call duration in cocaine animals, inducing aversivelike call properties and further suggesting that OXT may attenuate positive affective states. There were minimal differences in call bandwidth across groups and no significant differences in call amplitude. When assessing the ultrasonic vocalization's qualitative features, we found that cocaine led to an increased production of flat and short call types, both of which are associated with positive states, which were not attenuated by OXT. Altogether, we found that cocaine administration successfully produced a high affective state in female rats. Moreover, an OXT pretreatment was sufficient to decrease the rewarding effects of cocaine administration and therefore may play a vital role in treating those suffering from cocaine use disorder. (PsycInfo Database Record (c) 2026 APA, all rights reserved).
Aversion can arise from a combination of unconditioned stimuli that induce physical discomfort, such as pain and nausea. Chemotherapy-induced side effects, including taste and olfactory aversion, can persist even after treatment has ended, thereby reducing the quality of life. Currently, however, no effective pharmacological interventions exist for treating chemotherapy-induced conditioned aversion learning. Therefore, elucidating its underlying mechanisms is of great importance. In this study, we investigated cisplatin-induced olfactory aversion learning using the two-bottle choice test. Cisplatin was found to induce aversive responses to neutral odorants, namely isoamyl acetate and benzaldehyde. Notably, we obtained two key findings. First, an odor solution that was not aversive in the two-bottle choice test (i.e., distilled water) became aversive to mice when compared with a third novel odor solution that had not been presented in the test. Second, when pairs of three odorants were alternated over an extended period, the mice occasionally shifted their aversive responses as the pairings changed. In clinical practice, patients are exposed to a variety of odors. Thus, the new insights gained from this study on olfactory aversion may help inform the development of novel treatments for chemotherapy-related side effects. (PsycInfo Database Record (c) 2026 APA, all rights reserved).
Anxiety disorders emerging in adolescence are especially challenging to treat, partly due to adolescents having poor extinction recall and high relapse rates following exposure therapy, relative to other ages. Despite its clear clinical significance, little work has examined treatments to enhance extinction in adolescence. Dopamine, a key neurotransmitter involved in learning and memory, plays a critical role in fear extinction in adults, but its role in extinction in adolescents has not been well-explored. In a series of experiments, we investigated the effects of sulpiride, a dopamine antagonist, on extinction recall in male and female adolescent rats. Animals underwent Pavlovian fear conditioning followed by extinction training the next day, where animals were injected with either sulpiride or saline 15 min prior. On the next day animals were tested for their extinction recall. Sulpiride-treated male adolescents exhibited impaired extinction recall (Experiment 1), while sulpiride enhanced extinction recall in female adolescents (Experiment 2). However, these results were not replicated in a follow-up experiment that also included a sulpiride-no extinction control group (Experiment 3). Further, in contrast to what has been reported in past studies with adults, we did not observe any effect of sulpiride on adult female and male extinction recall (Experiment 4). Overall, these findings suggest that sulpiride may have sex-specific effects on extinction recall in adolescence, as has been reported in adults, though these effects appear to not be robust. (PsycInfo Database Record (c) 2026 APA, all rights reserved).
A previous study reported that explicitly unpairing a conditioned stimulus with an unconditioned stimulus generates the inhibitory property of the conditioned stimulus, as assessed by the retardation task, in an appetitive conditioning setting. This study conducted further experiments to demonstrate the conditioned inhibition induced by explicitly unpaired (EUP) training using the superconditioning and summation tests. In Phase 1, rats subjected to the EUP procedure received training in which light and food were explicitly unpaired. In Phase 2, rats in the EUP group for the superconditioning were trained with pairings of a light-tone compound and food. During the test phase, food-cup responses to either light or tone were measured. Food-cup responses to the tone in the EUP group were significantly higher than those in three control groups designed to rule out alternative explanations. For the summation test, rats in the EUP group underwent the same Phase 1 training as the superconditioning group, followed by Phase 2, which involved pairing the tone with food. In the test phase, food-cup responses to either the tone or the light + tone compound were measured. Food-cup responses to the tone in the EUP group were higher than those in the control group, but no difference was observed between the EUP and control groups for responses to the compound stimulus. These results indicate that EUP of the conditioned stimulus and unconditioned stimulus effectively generates superconditioning in appetitive conditioning. Superconditioning may provide a useful approach for investigating the neural mechanisms underlying appetitive conditioned inhibition. (PsycInfo Database Record (c) 2026 APA, all rights reserved).
Memories are dynamic and can be made vulnerable to disruption upon reactivation, resulting in a long-lasting attenuation of conditioned responses (i.e., cue-dependent amnesia). Traditionally, cue-dependent amnesia has been studied using AAA between-subjects designs, where a memory is trained for context A, reactivated, and tested with the same context. Using contextual fear conditioning in rats and midazolam as the amnestic agent, we have recently observed that amnesia can be observed when memories are reactivated by a generalization stimulus (context B) and tested with the same generalization stimulus (ABB design). However, this amnestic intervention does not affect the fear expression when animals are tested with the original stimulus (ABA design) or a novel generalization stimulus (ABC design). Methodologically, however, evaluating whether amnesia is reversed, rather than simply not expressed, requires tracking changes in responding within the same individuals across contexts and time. This avoids the ambiguity inherent to between-group comparisons, which may confound memory retention with retrieval differences driven by contextual or procedural variability. Here, using an ABB, ABA, and ABC within-subjects design and employing a gold standard amnestic manipulation-protein synthesis inhibition via cycloheximide-the interplay between memory retention and amnesia expression in different contexts was assessed. The results indicate that amnesia is expressed only when cycloheximide-animals are re-exposed to the reactivation context, regardless of when this re-exposure occurs within the experimental timeline. The implications of these findings for a reconsolidation-based account of postreactivation amnesia are discussed. (PsycInfo Database Record (c) 2026 APA, all rights reserved).
Early exposure to stress is associated with biological processes that precede cellular senescence and an increased risk of age-related diseases. Adolescence is a period of heightened susceptibility to social environment-related stressors. This developmental stage is also associated with the onset of psychiatric disorders and the adoption of behaviors that can affect long-term health trajectories. In this review, we aimed to assess the progress of rodent research on the relationship between adolescent social stress and later disease-related sequels and cellular senescence. We present a synthesis of 35 peer-reviewed articles indexed in PubMed before July 2025, selected from a web search based on the terms (social stress) AND (senescence OR DNA damage OR telomere OR inflammation) AND (adolescence OR juvenile OR youth OR early life) AND (mice OR mouse OR murine OR rat OR rodent). Adolescent social stress results in decreased social behaviors and increased anxietylike and depressionlike responses. In addition, enduring alterations in physiological responses to acute stress challenges and broad sequelae on neural, cardiovascular, endocrine, and gastrointestinal systems associated with inflammation were found. Sex differences in stress susceptibility were observed across all domains. However, despite the theoretical framework linking stress to aging, our synthesis reveals that direct evidence regarding telomere dynamics and DNA damage in this specific developmental window remains limited in rodent research. Consequently, this review provides an overview of biological mechanisms linking psychosocial stress during adolescence to chronic disease states while identifying the scarcity of direct senescence data as an important gap for future investigation. (PsycInfo Database Record (c) 2026 APA, all rights reserved).
Hospitalizations and deaths related to mental health disorders have increased in recent decades, highlighting the need for improved understanding of the neurocircuitry underlying cognitive dysfunction. Dysfunction in neural coordination between the hippocampus (HPC) and prefrontal cortex (PFC) is widely reported to be a signature of many mental health disorders. This circuit is crucial for many forms of adaptive behavior, with the nucleus reuniens (RE) of the thalamus hypothesized to be a critical hub that coordinates HPC-PFC interactions in the service of cognition. This study examined the role of the RE in associative memory by assessing the impact of its inactivation in male and female rats performing the Paired Associates Learning task, a touchscreen-based visuospatial memory paradigm with translational relevance for human mental health disorders. Using muscimol inactivation, we found that RE suppression significantly impaired Paired Associates Learning performance, supporting its role in HPC-PFC circuit coordination. Modulating nicotinic receptors in the RE with an agonist also produced significant deficits; however, we did not see any significant behavioral effects with an antagonist. These findings suggest that the RE is critical for Paired Associates Learning task performance, and its functional contribution may be modulated by cholinergic nicotinic signaling, but additional studies are necessary to test the robustness of this observation. Understanding RE's role in cognition may inform therapeutic strategies for psychiatric and neurological disorders characterized by HPC-PFC dysfunction. (PsycInfo Database Record (c) 2026 APA, all rights reserved).
Early life inflammation has long been associated with increased risk of later neuropsychiatric developmental disorder (NDD) diagnosis in humans. However, despite converging lines of evidence implicating the immune system in NDD etiology combined with reported sex differences in NDD diagnosis rates and the increasingly appreciated role of traditionally immune-associated factors in the sexual differentiation of the brain, a direct link connecting these three processes remains elusive. Here, we sought to characterize the enduring effects of early life inflammation in male and female rats exposed to the viral mimetic polyinosinic:polycytidylic acid (poly(I:C), 5 mg/kg) on Postnatal Day 8 (P8) and P10, a sensitive period we previously identified. We assessed a variety of behaviors-from juvenile social play to adult reward-guided decision making-and recorded from single neurons in nucleus accumbens as rats performed a task commonly used to assess cognitive control. All assessments were performed in the same animals allowing for exploratory factor analysis, which identified five factors that together reveal novel connections between behavioral measures across the lifespan and neural activity patterns. Collectively, this work suggests that viral-mediated inflammation at this developmental timepoint is not a robust risk factor for an NDD-like phenotype in rats. However, factor analysis revealed that sex and early life inflammation shifted two distinct modalities of rat "personality," highlighting the utility of combining modern neuroscience approaches with the study of complex, naturalistic behaviors. Future work should directly test these putative factor associations to determine the extent to which early life behavior may be predictive of adult cognition. (PsycInfo Database Record (c) 2026 APA, all rights reserved).
Social defeat (SD) is a well established model that increases addiction vulnerability accompanied by depressive- and anxiety-like behaviors. Environmental enrichment (EE) has been shown to enhance resilience and mitigate stress-induced behavioral alterations. Here, we investigated the protective effects of EE during adolescence, both before and during SD encounters, on stress-induced anxiety, depression and the increased conditioned rewarding effects of a subthreshold cocaine dose in adulthood. We employed the social interaction test (SIT) to categorize mice into resilient and susceptible phenotypes based on depressive-like behaviors. Anxiety was assessed using the elevated plus maze (EPM). EE did not alter the percentage of resilient and susceptible mice (33%-63% in standard housing vs. 46%-54% in EE), nor did it prevent stress-induced anxiety. Only defeated mice housed under standard conditions developed 1.5 mg/kg cocaine-induced conditioned place preference, whereas EE-exposed stressed mice did not acquire cocaine-induced conditioned place preference. Our findings highlight that EE during adolescence serves as a protective factor by promoting the development of a resilient phenotype in adulthood against increased drug reward. However, it was ineffective in counteracting depressive- and anxiety-like behaviors. (PsycInfo Database Record (c) 2026 APA, all rights reserved).
