Biology subjects

Rouzer, S. K.

Publications and source records attributed to Rouzer, S. K..

5 recordsLinked to original sources

bioRxiv2026

Prenatal alcohol and cannabinoid co-exposure increases ethanol-seeking in adult offspring and produces sex-dependent medial prefrontal cannabinoid receptor 1 expression.

Background: Alcohol and cannabinoids are frequently used during pregnancy, however their combined effects on offspring outcomes are currently under-investigated. In this study, co-exposure was compared to single-drug and drug-free exposures for influences on adult alcohol-seeking and cannabinoid system proteomics. Methods: Pregnant C57BL/6J mice received ethanol vapor (ALC), CP-55,940 (0.75 mg/kg; CB), both (ALC+CB), or neither on gestational days 12-15. Beginning on Postnatal Day 200, male and female offspring underwent home-cage ethanol drinking (N=108) and operant self-administration, progressive-ratio, extinction, and reinstatement testing (N=96). CNR1 and CNRIP1 protein abundance was quantified in the medial prefrontal cortex (mPFC) and dorsomedial striatum (N=57) and compared to within-subject drinking behaviors. Results: Prenatal CB exposure increased cumulative home-cage ethanol intake, primarily in males. At 40% ethanol under progressive-ratio schedules, ALC+CB males consumed more than all other male groups, whereas all exposed female groups consumed more than controls. ALC+CB males also showed greater extinction responding than all other male groups and greater reinstatement intake relative to baseline than CON and ALC males. ALC+CB increased mPFC CNR1 in males relative to all other groups, whereas CB and ALC+CB reduced mPFC CNR1 in females. Higher mPFC CNR1 was associated with fixed-ratio and 40% progressive-ratio intake, extinction, and reinstatement exclusively in males. Conclusions: Prenatal co-exposure produced a persistent male phenotype of enhanced ethanol seeking that was distinct from either exposure alone and accompanied by elevated mPFC CNR1. This behavioral and molecular convergence justifies future investigations manipulating corticostriatal cannabinoid signaling to attenuate exposure-induced ethanol consumption in late adulthood.

developmental biology↗

bioRxiv2025

Early Life Outcomes of Prenatal Exposure to Alcohol and Synthetic Cannabinoids in Mice

This study explores the effects of prenatal co-exposure to alcohol and synthetic cannabinoids on offspring viability, physical development, and neurobehavioral outcomes in young adulthood. The aim is to identify distinct outcomes of co-exposure compared to single-drug exposures and to examine potential sex-specific vulnerabilities in motor coordination and exploratory behaviors. Pregnant C57Bl/6J mice were assigned to one of four treatment groups: Control, Alcohol-exposed, Cannabinoid-exposed, or Alcohol+Cannabinoid-exposed, with drug administration occurring between Gestational Days 12-15. Offspring were first evaluated at birth for survival, physical malformations, and developmental delays. Subsequently, young adult offspring were assessed for motor coordination using rotarod tests and exploratory behavior using open field tests. Our results indicate that alcohol and cannabinoid co-exposure significantly reduced offspring survival and litter sizes compared to controls. Non-viable offspring displayed craniofacial abnormalities, limb malformations, and developmental delays. Behavioral assessments in young adulthood demonstrated that all forms of prenatal drug exposure impaired motor coordination in males, while alcohol and cannabinoid exposures independently produced impairments in females. In the open field test, co-exposed male offspring exhibited reduced center exploration, indicative of anxiety-like behavior. Co-exposed offspring, regardless of sex, demonstrated hyperactivity, characterized by increased speed and distance traveled. Together, these findings underscore the heightened risks associated with prenatal polysubstance exposure, which exacerbates offspring mortality and induces sex-specific neurobehavioral deficits. This study highlights the distinct outcomes associated with prenatal co-exposure, and the need for future research to investigate underlying mechanisms driving these developmental disruptions and sex-specific susceptibilities. Structured AbstractO_ST_ABSPurposeC_ST_ABSThis study investigates the effects of prenatal co-exposure to alcohol and synthetic cannabinoids on offspring viability, physical development, and neurobehavioral outcomes in young adulthood. The goal of this investigation is to determine whether prenatal co-exposure produces distinct outcomes from single-drug exposures, including sex-specific vulnerabilities in motor coordination and exploratory behaviors. MethodsPregnant C57Bl/6J mice were randomly assigned to one of four treatment groups: drug-free controls, alcohol (ALC)-exposed, cannabinoid (CP-55,940, CB)-exposed or ALC+CB-exposed, with drug exposure occurring between Gestational Days 12-15. Offspring viability, physical malformations, and developmental delays were first assessed at birth. Then, behavioral evaluations, including rotarod and open field tests, were conducted on young adult offspring (Postnatal Days 100-120). ResultsALC+CB exposure significantly decreased litter survival (p = 0.006) and offspring viability compared to controls. Non-viable offspring exhibited craniofacial abnormalities, limb malformations, and developmental delays. Assessments of rotarod performance revealed that all exposures reduced motor coordination in males compared to controls (p < 0.05), while ALC and CB exposures alone produced this outcome in females. Open field tests indicated that ALC+CB exposure reduced time in the center of the arena in male offspring exclusively, while this same exposure increased hyperactivity compared to single-drug and control groups, independent of sex (p < 0.05). ConclusionsPrenatal co-exposure to alcohol and synthetic cannabinoids exacerbates offspring mortality and induces sex-specific deficits in neurobehavioral motor outcomes. These findings highlight the distinct risks of polysubstance exposure during pregnancy and underscore the need for targeted interventions to mitigate the effects of prenatal polysubstance exposure on offspring health outcomes. HighlightsO_LIAlcohol and cannabinoid co-exposure significantly reduces offspring survival. C_LIO_LIReduced survival is associated with offspring craniofacial and limb malformations. C_LIO_LIPrenatal exposures produce sex-specific impairments in motor coordination. C_LIO_LICo-exposed offspring display hyperactivity in young adulthood. C_LI

animal behavior and cognition↗

bioRxiv2023

Reduced fetal cerebral blood flow following prenatal drug exposure predicts perinatal mortality.

BackgroundChildren exposed prenatally to alcohol or cannabinoids individually can exhibit growth deficits and increased risk for adverse birth outcomes. However, these drugs are often co-consumed and their combined effects on early brain development are virtually unknown. The blood vessels of the fetal brain emerge and mature during the neurogenic period to support nutritional needs of the rapidly growing brain. Teratogenic exposure during this gestational window may therefore impair fetal cerebrovascular development. ObjectiveTo determine whether prenatal polysubstance exposure confers additional risk for impaired fetal-directed blood flow and offspring viability compared to each drug individually. Study DesignWe performed high resolution in vivo ultrasound imaging in C57Bl/6J pregnant mice. After pregnancy confirmation, dams (n=40) were randomly assigned to one of four groups: drug-free control, alcohol-exposed, cannabinoid-exposed or alcohol-and-cannabinoid-exposed. Drug exposure occurred daily between Gestational Days 12-15, equivalent to the transition between the first and second trimesters in humans. Dams first received an intraperitoneal injection of either cannabinoid agonist CP-55940 (750{micro}g/kg) or volume-equivalent vehicle. Then, dams were placed in vapor chambers for 30min of inhalation of either ethanol or room air. Dams underwent ultrasound imaging on three days of pregnancy: Gestational Day 11 (pre-exposure), Gestational Day 13.5 (peri-exposure) and Gestational Day (post-exposure), and were subsequently monitored for health and delivery outcomes. ResultsOf all exposure groups, only dams co-exposed to both alcohol and cannabinoids experienced reduced gestational weight gain while undergoing drug treatments. These same co-exposed pregnant mice also demonstrated higher (+42mg/dL) blood ethanol concentrations than dams exposed to alcohol only. All drug exposures decreased fetal cranial blood flow 24-hours after the final exposure episode, though combined alcohol and cannabinoid reduced internal carotid artery blood flow relative to all other exposures. Umbilical artery metrics were not affected by drug exposure, indicating a specific vulnerability of fetal cranial circulation. Cannabinoid exposure significantly reduced cerebroplacental ratios, mirroring prior findings in marijuana-exposed human fetuses. Post-exposure cerebroplacental ratios significantly predicted subsequent perinatal mortality (p=0.019, area under the curve, 0.772; sensitivity, 81%; specificity, 85.70%) and retroactively diagnosed prior drug exposure (p=0.005; AUC, 0.861; sensitivity, 86.40%; specificity, 66.7%). Conclusion(s)Fetal cerebrovasculature is significantly impaired by exposure to alcohol or cannabinoids, and co-exposure confers additional risk for adverse birth outcomes. Considering the rising potency and global availability of cannabis products, there is an imperative for research to explore translational models of prenatal drug exposure, including polysubstance models, to inform appropriate strategies for treatment and care in pregnancies affected by drug exposure. Key PointsO_ST_ABSQuestionC_ST_ABSDoes simultaneous prenatal exposure to alcohol and cannabinoids present significant additional risk to fetal health compared to each drug individually? FindingsMaternal murine ultrasound analyses showed that alcohol and cannabinoid exposure, individually, reduced fetal cerebral arterial blood flow metrics. Notably, polysubstance-exposed fetuses demonstrate the worst cerebral hemodynamics, and reductions in fetal blood flow significantly predict subsequent perinatal offspring mortality. MeaningPrenatal drug exposure persistently reduces fetal-directed blood flow, which can disrupt normal embryonic growth and neural development, and polysubstance exposure augments deficits specifically in cerebral arterial blood flow.

developmental biology↗

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↗

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↗