Biology subjects

Caceres-Rodriguez, A.

Publications and source records attributed to Caceres-Rodriguez, A..

7 recordsLinked to original sources

bioRxiv2026

Automated pup-level analysis reveals distinct effects of prenatal CBD and THC exposure on maternal retrieval

This study examined how prenatal CBD and {Delta}9-tetrahydrocannabinol (THC) exposure affects maternal caregiving in C57BL/6J mice. We developed the Machine-Automated Scoring of the Pup Retrieval Test (MAS-PRT) to overcome limitations of manual behavioral scoring. MAS-PRT integrates Multi-Animal DeepLabCut for dam and pup tracking with Detectron2 for dynamic nest reconstruction. Validated against 170 manually annotated retrieval trials, the pipeline showed high concordance with manual measurements and enabled reproducible extraction of encounter latency, retrieval latency, and locomotor trajectories. Prenatal exposure did not impair general nest-building or overall home-cage maternal care. However, pups from both CBD and THC groups showed reduced body weight at postnatal day 5. Cox proportional hazards modeling revealed divergent effects by compound: CBD-exposed dams exhibited a weight-dependent increase in probability of encountering and retrieving lighter pups, independent of pup sex. Spatial tracking further showed that dams traversed significantly shorter total trajectories when retrieving female progeny exposed to either compound. Longitudinal trial-by-trial analysis indicated intact task acquisition in controls and CBD dams, whereas THC dams displayed a flattened learning curve driven by lower retrieval latencies on initial trials. Together, these findings indicate that prenatal cannabinoid exposure does not produce generalized disruption of maternal care but instead induces compound-specific alterations in maternal reactivity, retrieval kinematics, and learning dynamics.

animal behavior and cognition↗

bioRxiv2026

Compound and sex specific medial prefrontal cortex rewiring after prenatal THC and CBD exposure

The growing perception of cannabinoids as benign has increased perinatal exposure to both {Delta}9-tetrahydrocannabinol (THC) and cannabidiol (CBD), yet their long-term effects on prefrontal circuitry remain incompletely defined. Here we used whole-cell and field electrophysiology in adult mice (P100-140) of both sexes to compare how in utero exposure to THC or CBD (GD5-18) remodels layer-5 pyramidal neurons in the medial prefrontal cortex (mPFC). We quantified intrinsic excitability, excitatory and inhibitory synaptic transmission, the net E/I ratio, spontaneous excitatory and inhibitory currents kinetics, and canonical forms of synaptic plasticity (endocannabinoid-mediated LTD and NMDA-dependent LTP). Both cannabinoids shifted the adult mPFC toward a more pro-excitatory state: the E/I ratio was altered in a compound- and sex-dependent manner, and endocannabinoid-mediated LTD was abolished across groups. THC recapitulated previously reported deficits, producing male-specific increases in intrinsic excitability and accelerating excitatory current kinetics in females, demonstrating a conserved cross-species vulnerability of prefrontal circuits to gestational THC. CBD produced distinct signatures: female offspring showed marked increases in spontaneous excitatory event frequency and amplitude, indicating large-scale reorganization of excitatory and inhibitory inputs, while male offspring exhibited a selective and profound impairment of LTP. The combination of universal eLTD loss and CBD-specific LTP impairment in males yields a bidirectional loss of plasticity: an emergent synaptic rigidity in which circuits are unable to potentiate or depress effectively. Together, these convergent and divergent effects establish that prenatal exposure to THC and CBD produces lasting, sex-dependent rewiring of mPFC circuitry. Our results caution that the non-intoxicating profile of CBD does not preclude durable developmental impact and underscore the importance of considering both compound identity and sex when assessing the neurodevelopmental risks of perinatal cannabinoid exposure.

neuroscience↗

bioRxiv2025

Prenatal Cannabinoids Produce Sex Specific Changes in Risk Assessment and Shared Increases in Repetitive Behavior in Adult Offspring

The widespread perception of cannabinoids as harmless remedies has led to increasing use of both cannabidiol (CBD) and {Delta}9-tetrahydrocannabinol (THC) during pregnancy, yet their long-term impact on offspring behavior remains incompletely characterized. To directly compare these compounds, pregnant mice received daily CBD or THC (3 mg/kg, gestational days 5-18) and adult progeny of both sexes were evaluated (P90-120). To capture complementary dimensions of emotional and defensive responding, we employed the elevated plus maze (EPM) to quantify anxiety-related measures and ethological risk-assessment postures (e.g., stretch-attend) and the marble burying (MB) test to index repetitive/defensive behavior; together these assays provide convergent but distinct readouts that increase sensitivity to cannabinoid-induced effects. In the EPM, prenatal CBD exposure selectively increased stretch-attend postures in females, indicating heightened risk assessment; males were unaffected, and THC produced no comparable effect. Classical EPM indices--time in open or closed arms, preference for open-arms, and total distance traveled--were unchanged across groups, except that THC-exposed females exhibited hyperlocomotion. In contrast, marble burying was increased in both sexes following prenatal exposure to either CBD or THC, indicating a shared enhancement of repetitive/defensive responses. These results show that prenatal cannabinoid exposure yields enduring, sex-dependent alterations in adult behavior, with CBD selectively heightening female risk assessment and both cannabinoids increasing repetitive behavior across sexes, challenging the notion that CBD is a benign alternative to THC during gestation.

neuroscience↗

bioRxiv2024

Gestational CBD shapes insular cortex in adulthood

Many expectant mothers use CBD to alleviate symptoms like nausea, insomnia, anxiety, and pain, despite limited research on its long-term effects. However, CBD passes through the placenta, affecting fetal development and impacting offspring behavior. We investigated how prenatal CBD exposure affects the insular cortex (IC), a brain region involved in emotional processing and linked to psychiatric disorders. The IC is divided into two territories: the anterior IC (aIC), processing socioemotional signals, and the posterior IC (pIC), specializing in interoception and pain perception. Pyramidal neurons in the aIC and pIC exhibit sex-specific electrophysiological properties, including variations in excitability and the excitatory/inhibitory balance. We investigated ICs cellular properties and synaptic strength in the offspring of both sexes from mice exposed to low-dose CBD during gestation (E5-E18; 3mg/kg, s.c.). Prenatal CBD exposure induced sex-specific and territory-specific changes in the active and passive membrane properties, as well as intrinsic excitability and the excitatory/inhibitory balance, in the IC of adult offspring. The data indicate that in-utero CBD exposure disrupts IC neuronal development, leading to a loss of functional distinction between IC territories. These findings may have significant implications for understanding the effects of CBD on emotional behaviors in offspring.

neuroscience↗

bioRxiv2023

Sexual differences in neuronal and synaptic properties across subregions of the mouse insular cortex

BackgroundThe insular cortex (IC) plays a pivotal role in processing interoceptive and emotional information, offering insights into sex differences in behavior and cognition. The IC comprises two distinct subregions: the anterior insular cortex (aIC), that processes emotional and social signals, and the posterior insular cortex (pIC), specialized in interoception and perception of pain. Pyramidal projection neurons within the IC integrate multimodal sensory inputs, influencing behavior and cognition. Despite previous research focusing on neuronal connectivity and transcriptomics, there has been a gap in understanding pyramidal neurons characteristics across subregions and between sexes. MethodsAdult male and female C57Bl/6J mice were sacrificed and tissue containing the IC was collected for ex vivo slice electrophysiology recordings that examined baseline sex differences in synaptic plasticity and transmission within aIC and pIC subregions. ResultsClear differences emerged between aIC and pIC neurons in both males and females: aIC neurons exhibited distinctive features such as larger size, increased hyperpolarization, and a higher rheobase compared to their pIC counterparts. Furthermore, we observed variations in neuronal excitability linked to sex, with male pIC neurons displaying a greater level of excitability than their female counterparts. We also identified region-specific differences in excitatory and inhibitory synaptic activity and the balance between excitation and inhibition in both male and female mice. Adult females demonstrated greater synaptic strength and maximum response in the aIC compared to the pIC. Lastly, synaptic long-term potentiation occurred in both subregions in males but was specific to the aIC in females. ConclusionsWe conclude that there are sex differences in synaptic plasticity and excitatory transmission in IC subregions, and that distinct properties of IC pyramidal neurons between sexes could contribute to differences in behavior and cognition between males and females. Highlights- Distinctions specific to sex are present within subregions of the insular cortex (IC) in C57Bl/6J mice. - Pyramidal neurons in the anterior IC (aIC) exhibited larger size and distinct electrical properties. Adult females exhibited stronger synaptic responses in the aIC. - Conversely, male posterior insular cortex neurons displayed increased excitability. - Synaptic long-term potentiation was observed in both subregions in males, but it was exclusive to the aIC in females. - Sex-based variations in various aspects of excitatory transmission within IC subregions could contribute to differences in behavior and cognition between males and females. Plain language summaryThis study investigates differences in the insular cortex (IC), a region of the brain responsible for emotions and sensory perceptions, between male and female mice. The IC has two parts: the front (aIC) deals with emotions and social cues, while the back (pIC) is focused on sensing pain and bodily sensations. We examined specific brain cells called pyramidal neurons in both aIC and pIC and discovered noteworthy distinctions between these neurons in adult male and female mice. Firstly, aIC neurons were larger and had unique electrical properties in both male and female mice. Males had more excitable pIC neurons compared to females, indicating that their neurons were more likely to transmit signals. We also explored how these neurons communicate with each other through connections known as synapses. In adult females, the aIC had stronger connections than the pIC. Finally, we observed that specific types of basic synaptic learning occurred exclusively in males in the aIC. These findings underscore significant disparities in the IC between males and females, offering valuable insights into the potential reasons behind variations in behaviors and emotions between sexes.

neuroscience↗

bioRxiv2023

Cocaine-induced loss of LTD and social impairments are restored by fatty acid amide hydrolase inhibition

BackgroundA single usage of a drug of abuse can have lasting effects on both the brain and behavior, continuing even after the drug has been metabolized and eliminated from the body. A single dose of cocaine can abolish endocannabinoid-mediated long-term depression (eCB-LTD) in the nucleus accumbens (NAc) within 24 hours of administration. However, it is uncertain whether this altered neuroplasticity entails a behavioral deficit. MethodsOur study employed adult male mice to investigate the effects of a single dose of cocaine (20 mg/kg) on eCB-LTD, saccharin preference, and social interactions 24 hours after administration. We also examined the gene expression in components of the eCB system. The pharmacological increase of anandamide was evaluated using the fatty acid amide hydrolase (FAAH) inhibitor URB597 (1 mg/kg). ResultsAfter a single dose of cocaine, mice displayed altered plasticity, social interactions, and preference for saccharin and a reduction in mRNA levels of the anandamide-catabolizing enzyme NAPE-PLD. We discovered that the FAAH inhibitor URB597 (1 mg/kg) successfully reversed the cocaine-induced loss of eCB-LTD in the NAc and restored normal social interaction in cocaine-exposed mice, but it did not affect their saccharin preference. ConclusionsOverall, this research underlines the neuroplastic changes and subsequent behavioral alterations that occur after the initial use of cocaine, while also suggesting a potential role for anandamide in the early impairments caused by cocaine. The findings highlight the importance of understanding the mechanisms underlying the initiation of drug use and offer a potential therapeutic target.

neuroscience↗

bioRxiv2022

In utero exposure to cannabidiol disrupts select early-life behaviors in a sex-specific manner

Cannabidiol (CBD), one of the main components of cannabis, is generally considered safe, despite the lack of studies on the possible consequences of its consumption during critical periods of neurodevelopment, including prenatal life. Although CBD crosses the placenta and its use during pregnancy is steadily increasing, the impact of gestational CBD exposure on early life is unknown. Here, we combined behavioral exploration and deep learning to assess how in utero exposure to low doses of CBD alters pre-weaning behaviors in mouse pups of both sexes. The data reveal that pups from CBD-treated dams exhibit sex-specific alterations in weight growth, homing behavior, and the syllabic repertoire of ultrasonic vocalizations. Thus, prenatal CBD is associated with alterations in innate behavioral responses and communication skills.

neuroscience↗