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) 2025 APA, all rights reserved).

Gonadal hormones (e.g., estradiol and progesterone) influence response to, and preference for, drugs in females; however, how hormonal contraceptives, synthetic hormones that decrease gonadal hormone levels, affect drug preference is not known. The current experiment investigated whether oral administration of levonorgestrel (LNG), a synthetic progestin used in hormonal contraceptives, would lead to a reduction in amphetamine (AMPH) preference. Female rats were tested for their AMPH preference over 3 days (which also served as extinction sessions) after receiving oral administration of LNG (250 μg, 500 μg, or 2 mg) or during an estrous cycle stage associated with higher levels of gonadal hormones (i.e., proestrus/estrus). Our results show that AMPH preference was reduced for females on 500 μg and 2 mg of LNG across extinction sessions. Interestingly, only the 2 mg LNG dose led to a disruption in the naturally occurring estrous cycle. Uterine horn width, an index of estrogen exposure, was decreased in all LNG groups, but only the 500 μg and 2 mg LNG groups showed suppression of gonadal hormones, suggesting that both doses are sufficient for contraceptive use in rats. Our study demonstrates an effective and noninvasive oral LNG administration method in a rat model and further shows reduced AMPH preference by LNG. (PsycInfo Database Record (c) 2025 APA, all rights reserved).

Evidence has shown that sex differences affect the symptoms and the response to treatments in neuropsychiatric disorders, including posttraumatic stress disorder (PTSD). Extinction, as a therapeutic method, and reinstatement, as a method that facilitates shock-related memory retrieval, may also be affected by sex differences; however, evidence is sparse. The present study aimed to explore the potential role of sex differences in the effect of extinction and reinstatement on behavioral functions in a rat model of PTSD. Fear learning was induced by three consecutive footshocks (0.8 mA, 3 s, paired with three sounds) on Day 1. Extinction training (20 sounds without footshock) was done 1 hr and 24 hr after footshocks. Reinstatement was done on Day 3, or 10, or 20, or 30, by placing rat in a new context and delivering one footshock (0.8 mA, 3 s, no sound). Results showed that females were more responsive to extinction due to significant decreases in freezing behavior in comparison with males, while reinstatement had more effect to recall shock-related memory in males. Pain threshold was increased and extinction decreased it in both sexes. Locomotion was decreased in fear conditioning group in both sexes and in PTSD + extinction males, while it was not changed in PTSD + extinction females. Reinstatement on Day 3 decreased locomotion in males. Rearing was decreased and extinction restored it in both sexes. By contrast, reinstatement on Day 3 decreased rearing in males. In conclusion, we suggested that females are more responsive to extinction and less sensitive to reinstatement. On the contrary, males are sensitive to reinstatement. (PsycInfo Database Record (c) 2025 APA, all rights reserved).

Pituitary adenylate cyclase-activating polypeptide (PACAP, ADCYAP1) is a highly conserved neuropeptide that plays essential roles in numerous physiological functions, and central PACAP signaling has been associated with mechanisms regulating stress-induced psychopathologies. PACAP binds to several receptor subtypes, including PAC1 (ADCYAP1R1), VPAC1 (VIPR1), and VPAC2 (VIPR2), to activate several signaling cascades that can alter neuronal excitability and enhance indices of neuroplasticity, and much of our prior work has suggested that the anxiogenic effects of bed nucleus of the stria terminalis (BNST) PACAP depend on the activation of PAC1 receptors. To complement our previous work that evaluated the roles of BNST PACAP expression and secretion in anxiety-related responses, we employed in the current work chemogenetic approaches in male PAC1-Ires-Cre mice to directly and specifically modulate the activities of BNST PAC1 receptor-expressing neurons. Inhibition of BNST PAC1 receptor neuron activity with clozapine-N-oxide significantly increased open arm exploration without reducing total locomotor activity; conversely, stimulating BNST PAC1 receptor function significantly reduced open arm exploratory activities. In sum, these data are consistent with our prior work suggesting a key role for BNST PACAP receptor activation in anxiety and stress; further, these observations importantly clarify the neural circuits involved in anxiety-like behaviors. (PsycInfo Database Record (c) 2025 APA, all rights reserved).

Gaze is one of the primary experimental measures for studying cognitive development, especially in preverbal infants. However, the field is only beginning to develop a principled explanatory framework for making sense of the various factors affecting gaze. We approach this issue by addressing infant gaze from first principles, using rational information gathering. In particular, we revisit the influential descriptive account of Hunter and Ames (1988), which posits a set of regularities argued to govern how gaze preference for a stimulus changes with experience and other factors. When the Hunter and Ames's (1988) model is reconsidered from the perspective of rational information gathering (as recently also proposed by other authors), one feature of the model emerges as surprising: that preference for a stimulus is not monotonic with exposure. This claim, which has at least some empirical support, is in contrast to most statistical measures of informativeness, which strictly decline with experience. We present a normative, computational theory of visual exploration that rationalizes this and other features of the classic account. Our account suggests that Hunter and Ames's (1988) signature nonmonotonic pattern is a direct manifestation of a ubiquitous principle of the value of information in sequential tasks, other consequences of which have recently been observed in a range of settings including deliberation, exploration, curiosity, and boredom. This is that the value of information gathering, putatively driving gaze, depends on the interplay of a stimulus' informativeness (called gain, the focus of other rationally motivated accounts) with a second factor (called need) reflecting the estimated chance that information will be used in the future. This computational decomposition draws new connections between infant gaze and other cases of exploration, and offers novel, quantitative interpretations and predictions about the factors that may impact infant exploratory attention. (PsycInfo Database Record (c) 2025 APA, all rights reserved).

The ability to engage in everyday tasks, such as walking, requires the integration of cognitive and motor processes. How these processes integrate may be discernable through the relation of brain activity patterns to behavioral performance, particularly in the prefrontal cortex (PFC), examination of which has been restricted because of the limitations in experimental design. We related behavior (cognition, walking) to brain activity, as measured by functional near-infrared spectroscopy, under dual-task conditions (cognition while walking) in healthy young adults. Our probe design enabled us to examine eight regions of interest across PFC and motor cortex to identify key areas related to behavior. Healthy young adults (N = 19) engaged in standing cognition (Serial 3 subtraction), single-task walking, and dual-task walking. We used functional near-infrared spectroscopy to identify regions associated with increases or decreases in activity under dual-task relative to the other conditions. We observed differences in brain activity patterns by task across multiple regions of interest, mostly in PFC. Specifically, more lateral regions were related to attention-demanding tasks, whereas motor tasks were related to relatively medial regions. Our results relate behavior to brain activity, as measured by functional near-infrared spectroscopy, under dual-task conditions. Our finding of relatively lateral PFC activity during attention-demanding tasks provides insights into behavioral and brain processes during experimental analogues of everyday activity, bringing us closer to understanding behavior-brain relations in the real world. (PsycInfo Database Record (c) 2025 APA, all rights reserved).

This study investigated whether 221 undergraduates (123 males, 98 females) with varying levels of cannabis use displayed a conditioned place preference (CPP) for a virtual reality (VR) room that previously contained virtual cannabis stimuli compared to a neutral VR room that was not paired with cannabis cues. We hypothesized that cannabis-using participants (n = 180) would spend a greater amount of time in, report greater subjective enjoyment in, and explicitly prefer a VR room that was previously paired with virtual cannabis stimuli relative to a neutral room, while participants with nonuse (n = 41) would not. Overall, participants did not demonstrate an implicit or explicit CPP for a VR room that was previously paired with cannabis cues. Interestingly, however, participants with recent cannabis use (n = 41) exhibited a significant implicit CPP for the cannabis-cue-paired VR room, while participants with nonrecent cannabis use (n = 113) did not. Furthermore, relative to males with cannabis use (n = 93), females with cannabis use (n = 87) demonstrated a significant explicit CPP for the cannabis-cue-paired context as well as significantly greater cannabis cravings. These findings elucidate the need for further research on the role of acute cannabis intoxication, sex, and cue-induced cravings in modulating CPP for cannabis-associated contexts. (PsycInfo Database Record (c) 2025 APA, all rights reserved).

Environmental threats are typically encountered when animals are searching for food and other necessities. Adaptive behavior must balance competition between fear behavior and reward seeking. We gave rats local neuronal deletions of the ventral pallidum (VP) or specifically deleted paraventricular thalamic nucleus (PVT) neurons projecting directly to the VP. Rats were then assessed in a conditioned suppression procedure in which cues predicting unique foot shock probabilities were presented during, but independent from, reward seeking. Foot shock introduction generally suppressed reward seeking in rats, and recovery from shock introduction was facilitated in rats with VP or PVT → VP pathway deletions. Discriminative fear was observed in controls, and this fear responding reduced over a single extinction session. VP deletion enhanced extinction fear responding, and PVT → VP pathway deletion abolished within-session fear reductions. The results demonstrate the VP and its inputs from the PVT shape reward seeking in threat settings and govern fear extinction responding. (PsycInfo Database Record (c) 2025 APA, all rights reserved).

The mechanisms responsible for individual differences in cognition are not well understood. This study assessed behavioral performance and magnetic resonance imaging (MRI)-derived brain volumes in male Fischer 344 young (6 months), middle-aged (15 months), and aged (23 months) adult rats and asked two primary questions: Do individual differences in spatial performance predict behavior in other cognitive domains? Are the observed differences in cognition related to the volume of brain areas responsible for these cognitive processes? Several cognitive domains were examined here along with MRI-derived volumetric measures of the hippocampus and neocortex. The tasks assessed spatial reference and working memory, and temporal ordering and spatial location novelty tasks. The hippocampus-dependent spatial version of the Morris watermaze was used to categorize each rat into high, average, and low performers within each age group. When scores on the spatial working memory task were compared to the spatial reference memory task, only young adults showed a positive relationship between performance on these tasks; this relationship was not apparent in the older animals. With respect to MRI measurements, differences were found in total intracranial volume and total brain volume across age, but there were no statistically significant relationships found across age or between cognitive categories in the neocortex or hippocampus cornu ammonis subfields. Three primary conclusions can be drawn: There is large variability in spatial memory across all ages, high performance on one cognitive domain does not necessarily predict high performance on another, and finally, finer structural analyses may be required to identify brain changes responsible for the individual differences observed here. (PsycInfo Database Record (c) 2025 APA, all rights reserved).