Biology subjects

Diaz, M. R.

Publications and source records attributed to Diaz, M. R..

15 recordsLinked to original sources

bioRxiv2026

Age- and sex- dependent effects of moderate gestational day 12 prenatal alcohol exposure on anxiety-like behaviors, ethanol intake, and mechanical sensitivity

RationalePrenatal alcohol exposure (PAE) can result in Fetal Alcohol Spectrum Disorder (FASD), which consists of a group of diagnosable medical conditions that can include an increased risk for anxiety disorders and/or alcohol misuse, and sensory issues, such as increased mechanical sensitivity. ObjectiveThis study investigated how a single moderate PAE on gestational day 12 (G12) alters anxiety-like behavior, ethanol (EtOH) intake, and mechanical sensitivity across the lifespan of Sprague Dawley rats. MethodsPregnant dams were exposed to vaporized EtOH or room air (control) for 6 hours (BECs [~]108 mg/dL). Testing in male and female offspring began at three different ages: juveniles ([~]postnatal day (P) 25), adolescents ([~]P45) and adults ([~]P80). ResultsThe greatest PAE effects were observed in adolescent animals, with alterations in anxiety-like behaviors demonstrated in the light-dark box and elevated plus maze. Additionally, adolescent female animals consumed more sweetened EtOH compared to males. However, PAE adolescent animals consuming less sweetened EtOH compared to their counterparts, which was also observed in adult PAE females. Interestingly, this effect is reversed in juvenile and adolescent males when tested with unsweetened EtOH, with juvenile females consuming more EtOH also. Finally, PAE and air animals exhibited increased mechanical sensitivity following post-natal EtOH consumption across all ages. ConclusionThese data demonstrate that there are age- and sex-specific effects of PAE on anxiety-like behaviors, EtOH intake, and mechanical sensitivity that are more distinct in adolescent animals.

neuroscience↗

bioRxiv2025

Moderate prenatal alcohol exposure differentially alters acute ethanol sensitivity of GABAergic transmission in CRFR1- and CRFR1+ CeM neurons

AbstractPrenatal exposure to alcohol (PAE) increases the risk for misusing alcohol and/or developing an alcohol use disorder (AUD) by adulthood. The corticotropin releasing factor (CRF) system is a major target of pre- and post-natal ethanol (EtOH) exposure. CRF and its receptor (CRFR1), in part, mediate EtOH potentiated GABA release in the medial nucleus of the central amygdala (CeM) of adult male rodents. Interestingly, our lab has shown a disruption in the function and expression of CeM CRFR1 and acute EtOHs effects on GABA transmission in PAE adolescent animals, but it is unknown whether these alterations to the CRF system persist into adulthood or alter the actions of acute EtOH on GABAergic transmission in the CeM. Using CRF1-Cre-tdTomato rats, this study examined how moderate PAE alters acute EtOH modulation of GABAergic neurotransmission onto CRFR1+ and CRFR1-CeM neurons in adult offspring (P80-105). Pregnant dams were exposed to vaporized ethanol or room air (control) on gestational day 12 (G12) for 6 hours and whole-cell electrophysiology was performed in the CeM to assess the actions of acute EtOH (44, 66, & 88 mM) on GABAergic transmission onto CRFR1+ and CRFR1-neurons. We found unique effects of PAE that were cell type- and concentration-dependent in males and females, suggesting PAE dysregulates acute EtOHs modulation of GABA transmission within the CeM in a sex-specific manner. This study contributes to the expanding body of research exploring the effects of PAE and how a single exposure can impact neurophysiological mechanisms in brain regions associated with AUD. HighlightsO_LIModerate PAE alters the actions of alcohol on synaptic transmission in adult rats C_LIO_LIPAE differentially impacts GABAergic transmission onto CeM CRFR1- and CRFR1+ C_LIO_LILong-term PAE effects in the CeM are sex-specific C_LI

neuroscience↗

bioRxiv2024

Moderate prenatal alcohol exposure alters GABAergic transmission and the action of acute alcohol in the CeM of adolescent rats

Individuals with prenatal alcohol exposure (PAE) are at a higher risk for developing alcohol use disorder (AUD). Using a rat model of PAE on gestational day 12 (G12; ~2nd trimesters in humans), a critical period for amygdala development, we have shown disruptions in medial central amygdala (CeM) function, an important brain region associated with the development of AUD. In addition to this, acute ethanol (EtOH) increases GABA transmission in the CeM of rodents in a sex-dependent manner, a mechanism that potentially contributes to alcohol misuse. How PAE alters acute alcohols effects within the CeM is unknown. Given these findings, we investigated how PAE may interact with acute alcohol to alter neuronal and synaptic mechanisms in the CeM of adolescent rats in order to understand PAE-induced alcohol-related behaviors. Under basal conditions, PAE males showed reduced rheobase, indicative of reduced excitability, and females showed a reduction in GABA transmission, indicated by lower spontaneous inhibitory postsynaptic currents (sIPSCs). We found that acute EtOH increased sIPSCs in control males at a moderate concentration (66 mM), while PAE males showed increased sIPSCs only at a high concentration (88 mM). Adolescent females, regardless of PAE status, were largely insensitive to EtOHs effects at all tested concentrations. However, PAE females showed a significant increase in sIPSCs at the highest concentration (88 mM). Overall, these findings support the hypothesis that PAE leads to sex-specific changes in synaptic activity and neuronal function. Future research is needed to better understand the specific mechanisms by which acute EtOHs affects neurotransmission in the adolescent brain of individuals with a history of PAE.

neuroscience↗

bioRxiv2024

Erythrocyte membrane protein 3 (EMAP3) is exposed on the surface of the Plasmodium berghei infected red blood cell

The human malaria parasite Plasmodium falciparum invades red blood cells (RBC) and exports parasite proteins to transform the host cell for its survival. These exported proteins facilitate uptake of nutrients and cytoadherence of the infected RBC (iRBC) to endothelial cells of small blood vessels, thus protecting the iRBC from splenic clearance. The parasite protein PfEMP1 and the host protein CD36 play a major role in P. falciparum iRBC cytoadherence. The murine parasite Plasmodium berghei is a widely used experimental model that combines high genetic tractability with access to in vivo studies. P. berghei iRBC also sequesters in small blood vessels, mediated by binding to CD36. However, the parasite proteins binding to CD36 are unknown and only very few parasite proteins, including EMAP1 and EMAP2, have been identified that are present at the iRBC membrane. We have identified a new protein named EMAP3 and demonstrated its export to the iRBC membrane where it interacts with EMAP1, with only EMAP3 exposed on the outer surface of the iRBC. Parasites lacking EMAP3 display no significant reduction in growth or sequestration, indicating that EMAP3 is not the major CD36-binding protein. The outer-surface location of EMAP3 offers a new scaffold for displaying P. falciparum proteins on the surface of the P. berghei iRBC, providing a platform to screen in vivo putative inhibitors of P. falciparum cytoadherence.

microbiology↗

bioRxiv2023

A multi-strategy antimicrobial discovery approach reveals new ways to combat Chlamydia

While the excessive use of broad-spectrum antibiotics is a major driver of the global antibiotic resistance crisis, more selective therapies remain unavailable for the majority of bacterial pathogens. This includes Chlamydia spp., which cause millions of urogenital, ocular, and respiratory infections each year. We here report major conceptual additions to the available toolkit for antichlamydial discovery, including both experimental and computational approaches. Moreover, we report the to date most comprehensive search of the chemical space for novel antichlamydial activities, which identified over sixty compounds that are chemically diverse, structurally different from known antibiotics, non-toxic to human cells, and highly potent in blocking Chlamydia growth. While some compounds caused a reversible block in Chlamydia development, others could eradicate both established and persistent infections in a bactericidal manner. The most potent antichlamydials displayed compelling selectivity, some also synergies with clinically used antibiotics, as well as interactions profiles enabling predictions of molecular modes of action. Moreover, one compound displayed reduced antichlamydial efficacy in autophagy-deficient cells, suggesting a host- targeted activity. Altogether, we suggest that these novel antichlamydials could serve as tools for advancing our understanding of Chlamydia biology and as chemical starting points for developing more sustainable therapeutics for one of the most successful groups of intracellular pathogens.

microbiology↗

bioRxiv2023

Prenatal Methadone Exposure Leads To Disruptions In Adult-Born Dentate Granule Cell Survival And Female Persistent Fear Responding

Methadone is used for the treatment of opioid use disorder, including in pregnant patients. Research has established several consequences of prenatal exposure to misused opioids, however little work has investigated the effects of prenatal methadone exposure (PME) on the offspring long-term, despite the continued prescription to pregnant individuals. The current study aimed to identify the long-term cognitive impairments arising from PME and assess hippocampal neurogenesis in these adult offspring. Pregnant Sprague Dawley rats were injected with methadone or sterile water twice daily from gestational day 3-20 or were left undisturbed as naive controls. Adult offspring were tested in one of three behavioral tasks to assess pattern separation, spatial learning and memory, and contextual learning and memory, or were assigned to hippocampal tissue collection. For assessment of neurogenesis, offspring underwent injections of bromodeoxyuridine, and brains were collected at 24hr, 2wks, or 4wks for immunofluorescent staining. Methadone-exposed females, but not males, showed subtle impairments in pattern separation and heightened freezing during the extinction period in the fear conditioning task, and spatial memory in both sexes remained unaffected. Additionally, PME did not alter the rate of dentate granule cell proliferation but did significantly reduce the number of adult-born neuron surviving to a mature phenotype in the PME females at the 4wk timepoint. This work adds to the understanding of PME on offspring long-term and demonstrates female-specific sensitivity to these consequences. Future work is needed to fully investigate the neural disruptions arising from PME, with the goal of better supporting exposed individuals long-term.

neuroscience↗

bioRxiv2022

Gestational day 12 moderate prenatal alcohol exposure produces sex-specific social impairments and attenuates prelimbic excitability and amygdala-cortex modulation of adult social behavior.

Lifelong social impairments are common in individuals with prenatal alcohol exposure (PAE), and preclinical studies have identified gestational day (G)12 as a vulnerable timepoint for producing social deficits following binge-level PAE. While moderate (m)PAE also produces social impairments, the long-term neuroadaptations underlying them are poorly understood. Activity of the projection from the basolateral amygdala to the prelimbic cortex (BLA[->]PL) leads to social avoidance, and the PL alone is implicated in negative social behaviors, making each of these potential candidates for the neuroadaptations underlying mPAE-induced social impairments. To examine this, we first established that G12 mPAE produced sex-specific social impairments lasting into adulthood. We then chemogenetically inhibited the BLA[->]PL using Clozapine N-Oxide (CNO) during adult social testing. This revealed that CNO reduced social investigation in control males, but had no effect on mPAE males or females of either exposure, indicating that mPAE attenuated the role of this projection in regulating male social behavior and highlighting one potential mechanism by which mPAE affects male social behavior more severely. Using whole-cell electrophysiology, we also examined mPAE-induced changes to PL pyramidal cell physiology and determined that mPAE reduced the excitability of these cells, likely due to increased suppression by inhibitory interneurons. Overall, this work identified two mPAE-induced neuroadaptations that last into adulthood and which may underlie the sexspecific vulnerability to mPAE-induced social impairments. Future research is necessary to expand upon how these circuits modulate both normal and pathological social behavior, and to identify sex-specific mechanisms leading to differential vulnerability in males and females.

neuroscience↗

bioRxiv2022

Prenatal methadone exposure leads to long-term memory impairments and disruptions of dentate granule cell function in a sex-dependent manner

Prenatal opioid exposures lead to extensive cognitive and emotion-regulation problems in children, persisting at least through school-age. Methadone, an opioid typically used for the treatment of opioid use disorder, has been approved for use in pregnant women for several decades. Importantly, however, the impacts of prenatal methadone exposure (PME), particularly on offspring as they progress into adulthood, has not been extensively examined. In recent years, children and young animal models have shown cognitive deficits related to PME, including evidence of hippocampal dysfunction. The present work aims to examine the persistent nature of these deficits, as well as determine how they may differ by sex. Pregnant Sprague Dawley rats either received subcutaneous methadone or water injections twice daily from gestational days 3-20 or were left undisturbed. Following postnatal day 70, male and female offspring were behaviorally tested for impairments in recognition memory using the Novel Object Recognition task and working spatial memory through Spontaneous Alternation. Additionally, using whole-cell patch-clamp electrophysiology, hippocampal dentate granule cell function was examined in adult offspring. Results indicate that methadone-exposed females showed decreased excitability and increased inhibition of these dentate granule cells, while males did not. These findings were accompanied by impairments in female working spatial memory and impaired recognition memory of both sexes. Overall, this work supports the continued investigation of the long-term effects of PME on adult male and female learning and memory, as well as promotes further exploration of adult hippocampal function as a neural mechanism impacted by this exposure.

neuroscience↗

bioRxiv2021

Moderate prenatal alcohol exposure modifies sex-specific CRFR1 activity in the central amygdala and anxiety-like behavior in adolescent offspring.

Anxiety disorders are highly prevalent among individuals with a history of prenatal alcohol exposure (PAE), and adolescent rodents demonstrate anxiety-like behavior following moderate PAE on Gestational Day (G) 12. A likely systemic target of PAE is the stress peptide corticotrophin-releasing factor (CRF), as activation of CRF receptor 1 (CRFR1) in the medial nucleus of the central amygdala (CeM) is known to increase anxiety-like behavior in adults. To determine if CRF-CRFR1 interactions underly PAE-induced anxiety, functional changes in CRF system activity were investigated in adolescent male and female Sprague Dawley rats following G12 PAE. Compared to air-exposed controls, PAE increased basal spontaneous (s) inhibitory post-synaptic current (IPSC) frequency in the CeM of males, but not females. Furthermore, PAE blunted CRFR1-regulated miniature (m) IPSCs in a sex- and dose-specific manner, and only PAE males demonstrated tonic CRFR1 activity in the CeM. It was further determined that G12 PAE decreased CRFR1 mRNA in the CeM of males while increasing regional expression in females. Finally, infusion of a CRFR1 agonist into the CeM of adolescents produced a blunted expression of CRFR1-induced anxiety-like behavior exclusively in PAE males, mirroring the blunted physiology demonstrated by PAE males. Cumulatively, these data suggest that CRFR1 function within the CeM is age- and sex-specific, and PAE not only increases the expression of anxiety-like behavior, but may reduce the efficacy of treatment for PAE-induced anxiety through CRFR1-associated mechanisms. Therefore, future research will be necessary to develop targeted treatment of anxiety disorders in individuals with a history of PAE.

neuroscience↗

bioRxiv2021

RNA-Seq analysis and transcriptome assembly of Salicornia neei reveals powerful system for ammonium detoxification

BackgroundSalicornia neei is a halophyte plant that has been proposed for use in the phytoremediation of the saline wastewater generated by land-based aquaculture, which usually contains elevated concentrations of ammonium resulting from protein metabolism. To identify the molecular mechanisms related to ammonium response, we analyzed the transcriptome of S. neei in response to growth in saline water containing 3 mM ammonium and the Michaelis-Menten ammonium removal biokinetics. ResultsThe RNA sequencing generated a total of 14,680,108 paired-end reads from the control and stressed conditions. De novo assembly using the CLC Genomic Workbench produced 86,020 transcripts and a reference transcriptome with an N50 of 683 bp. A total of 45,327 genes were annotated, representing 51.2% of the contig predicted from de novo assembly. As regards DEGs, a total of 9,140 genes were differentially expressed in response to ammonium in saline water; of these, 7,396 could be annotated against functional databases. The upregulated genes were mainly involved in cell wall biosynthesis, transmembrane transport and antiporter activities, including biological KEGG pathways linked to the biosynthesis of secondary metabolites, plant hormone signal transduction, autophagy, and nitrogen metabolism. In addiction, a set of 72 genes was directly involved in ammonium metabolism, including glutamine synthetase 1 (GLN1), glutamate synthase 1 (GLT1), and ferredoxin-dependent glutamate synthase chloroplastic (Fd-GOGAT). Finally, we observed that the ammonium uptake rate increased with increasing ammonium concentrations, and tended toward saturation in the range of 3 to 4 mM. ConclusionOur results support the hypothesis that an ammonium detoxification system mediated by glutamine and glutamate synthase was activated in S. neei when exposed to ammonium and saline water. The present transcriptome profiling method could be useful when investigating the response of halophyte plants to saline wastewater from land-based aquaculture.

genomics↗

bioRxiv2020

Efficiency of Salicornia neei in removing nitrogen and producing biomass from a hypersaline and artificial wetland to treat aquaculture effluent

In this study we evaluated the potential of Salicornia neei, a halophyte plant native to South America, to treat saline effluents with simulated concentration of ammonium-N (Amm) and nitrate-N (Nit) similar to land-based marine aquaculture effluents. Plants were cultivated for 74 days in drainage lysimeters under three treatments of seawater fertilized with: 1) Nit+Amm, 2) Nit, or 3) without fertilizer (Control). Over 5 repetitions, nitrogen removal efficiency (RE) was high in both treatments (Nit + Amm = 89.6{+/-} 1,0 %; Nit 88.8 {+/-} 0.9 %). While nitrogen removal rate (RR) was non linear and concentration-dependent (RRday 1-4: Nit+Amm= 2.9 {+/-} 0.3 mg L-1 d-1, Nit = 2.4 {+/-} 0.5mg L-1 d-1; RRday5-8: Nit + Amm = 0.8 {+/-} 0.2mg L-1 d-1, Nit=1.0 {+/-} 0.2mg L-1 d-1). Effluent salinity increased from 40.6 to 49.4 g L-1 during the experiment, with no observed detrimental effects on RE or RR. High nitrogen removal efficiency and significant biomass production observed, Nit+Amm = 11.3 {+/-} 2.0 kg m-2; Nit = 10.0 {+/-} 0.8 kg m-2; Control = 4.6 {+/-} 0.6 kg m-2, demonstrate that artificial wetlands of S. neei can be used for wastewater treatment in saline aquaculture in South America.

plant biology↗

bioRxiv2020

Factors of sex and age dictate the regulation of GABAergic activity by corticotropin-releasing factor receptor 1 in the medial sub-nucleus of the central amygdala.

Adolescents are phenotypically characterized with hyper-sensitivity to stress and inappropriate response to stress-inducing events. Despite behavioral distinctions from adults, investigations of developmental shifts in the function of stress peptide corticotrophin-releasing factor (CRF) are generally limited. Rodent models have determined that CRF receptor 1 (CRFR1) activation within the central amygdala is associated with a stress response and induces increased GABAergic synaptic neurotransmission within adult males. To investigate age-specific function of this system, we performed whole-cell patch clamp electrophysiology in brain slices from naive adolescent (postnatal days (P) 40-49) and adult (>P70) male and female Sprague Dawley rats to assess GABAergic activity in the medial central amygdala (CeM). Our results indicate a dynamic influence of age and sex on neuronal excitability within this region, as well as basal spontaneous and miniature (m) inhibitory post-synaptic currents (IPSCs) in the CeM. In addition to replicating prior findings of CRFR1-regulated increases in mIPSC frequency in adult males, we found that the selective CRFR1 agonist, Stressin-1, attenuated mIPSC frequency in adolescent males, at a concentration that did not affect adult males. Importantly, this age-specific distinction was absent in females, as Stressin-1 attenuated mIPSC frequency in both adolescent and adult females. Finally, only adult males exhibited an increase in mIPSC frequency in response to the CRF1R antagonist, NBI 35965, suggestive of tonic CRFR1 activation in the CeM of adult males. Together, these data emphasize the robust influence of age and sex on neurophysiological function of a brain region involved in the production of the stress response.

neuroscience↗

bioRxiv2020

Moderate adolescent chronic intermittent ethanol exposure sex-dependently disrupts synaptic transmission and kappa opioid receptor function in the basolateral amygdala of adult rats

Adolescent alcohol exposure is associated with many negative outcomes that persist into adulthood, including altered affective and reward-related behaviors. However, the long-term neurological disruptions underlying these behavioral states are not fully understood. The basolateral amygdala (BLA) plays a critical role in many of these behaviors, and shifts in the excitatory/inhibitory balance in this area are capable of directly modulating their expression. While changes to BLA physiology have been demonstrated during the acute withdrawal phase following adolescent ethanol exposure, no studies to date have examined whether these persist long-term. The kappa opioid receptor (KOR) system is a neuromodulatory system that acts as a prominent mediator of negative affective behaviors, and alterations of this system have been implicated in the behavioral profile caused by chronic alcohol exposure in adulthood. Notably, in the BLA, the KOR system undergoes functional changes between adolescence and adulthood, but whether BLA KORs are functionally disrupted by adolescent ethanol exposure has not been examined. In this study, we exposed male and female Sprague-Dawley rats to a vapor inhalation model of moderate adolescent chronic intermittent ethanol (aCIE) and examined the long-term effects on GABAergic and glutamatergic neurotransmission within the adult BLA using whole-cell patch-clamp electrophysiology. We also assessed how KOR activation modulated these neurotransmitter systems in aCIE versus control rats using the selective KOR agonist, U69593. This investigation revealed that aCIE exposure disrupted basal glutamate transmission in females by increasing spontaneous excitatory postsynaptic current (sEPSC) frequency, while having no effects on glutamate transmission in males or GABA transmission in either sex. Interestingly, we also found that aCIE exposure unmasked a KOR-mediated suppression of spontaneous inhibitory postsynaptic current (sIPSC) frequency and sEPSC amplitude only in males, with no effects of aCIE exposure on KOR function in females. Together, these data suggest that moderate-level adolescent ethanol exposure produces long-term changes to BLA physiology and BLA KOR function, and that these changes are sex-dependent. This is the first study to examine persistent adaptations to both BLA physiology and KOR function following adolescent alcohol exposure, and opens a broad avenue for future investigation into other neurobiological and behavioral consequences of adolescent ethanol exposure-induced disruptions of these systems.

neuroscience↗

bioRxiv2020

Increased Ethanol Intake is Associated with Social Anxiety in Offspring Exposed to Ethanol on Gestational Day 12

Prenatal alcohol exposure (PAE) can result in physical, cognitive, and neurological deficits termed Fetal Alcohol Spectrum Disorder (FASD). Deficits in social functioning associated with PAE are frequently observed and persist throughout the lifespan. Social impairments, such as social anxiety, are associated with increased alcohol abuse, which is also highly pervasive following PAE. Yet, the relationship between PAE-induced social alterations and alcohol intake later in life is not well understood. In order to test this relationship, we exposed pregnant female Sprague Dawley rats to a single instance of PAE on gestational day 12 and tested offspring in adulthood (postnatal day 63) in a modified social interaction test followed by alternating alone and social ethanol intake sessions. Consistent with our previous findings, we found that, in general, PAE reduced social preference (measure of social anxiety-like behavior) in female but not male adults. However, ethanol intake was significantly higher in the PAE group regardless of sex. When dividing subjects according to level of social anxiety-like behavior (low, medium, or high), PAE males (under both drinking contexts) and control females (under the social drinking context) with a high social anxiety phenotype showed the highest level of ethanol intake. Taken together, these data indicate that PAE differentially affects the interactions between social anxiety, ethanol intake, and drinking context in males and females. These findings extend our understanding of the complexity and persistence of PAEs sex-dependent effects into adulthood.

neuroscience↗

bioRxiv2019

Adolescent forced swim stress increases social anxiety-like behaviors and alters the dynorphin/kappa opioid receptor system in the basolateral amygdala of males

Adolescence is a developmental period marked by robust neural alterations and heightened vulnerability to stress, a factor that is highly associated with increased risk for emotional processing deficits, such as anxiety. Stress-induced upregulation of the dynorphin/kappa opioid receptor (DYN/KOR) system is thought to, in part, underlie the negative affect associated with stress. The basolateral amygdala (BLA) is a key structure involved in anxiety, and neuromodulatory systems, such as the DYN/KOR system, can 1) regulate BLA neural activity in an age-dependent manner in stress-naive animals and 2) underlie stress-induced anxiety in adults. However, the role of the DYN/KOR system in modulating stress-induced anxiety in adolescents is unknown. To test this, we examined the impact of an acute, 2-day forced swim stress (FSS - 10 min each day) on adolescent (~postnatal day (P) 35) and adult Sprague-Dawley rats (~P70), followed by behavioral, molecular and electrophysiological assessment 24 hours following FSS. Adolescent males, but not adult males or females of either age, demonstrated social anxiety-like behavioral alterations indexed via significantly reduced social investigation and preference when tested 24 hours following FSS. Conversely, adult males exhibited increased social preference. While there were no FSS-induced changes in expression of genes related to the DYN/KOR system in the BLA, these behavioral alterations were associated with a robust switch in BLA KOR function. Specifically, while the KOR agonist, U69593, significantly increased GABA transmission in the BLA of non-stressed adolescent males, U69593 significantly inhibited BLA GABA transmission in stressed adolescent males, consistent with the observed anxiogenic phenotype in stressed adolescent males. This is the first study to demonstrate a KOR-dependent mechanism that may contribute to stress-induced social anxiety in adolescent males. Importantly, these findings provide evidence for potential KOR-dependent mechanisms that may contribute to pathophysiological interactions with subsequent stress challenges.

neuroscience↗