Biology subjects

Vulchanova, L.

Publications and source records attributed to Vulchanova, L..

3 recordsLinked to original sources

bioRxiv2025

VGF in the Nucleus Accumbens Regulates Synaptic and Opioid-Evoked Plasticity

Neuropeptides contribute to the functional complexity of the nucleus accumbens, and evaluating the mechanisms by which they influence reward neurocircuitry may reveal novel therapeutic targets. In this study, we investigated the role of the neuropeptide precursor VGF (non-acronymic) in the nucleus accumbens, and its contribution to synaptic and opioid-evoked plasticity and behavior. We first characterized VGF expression within the nucleus accumbens, then examined its impact on excitatory synaptic transmission, and finally disrupted its expression to assess its influence on opioid sensitivity. We found that VGF is expressed by interneurons and medium spiny neurons in the nucleus accumbens, and the VGF-derived peptide TLQP-62 reduced excitatory synaptic transmission onto nucleus accumbens medium spiny neurons. Conditional genetic knockout of VGF from the nucleus accumbens did not affect acute opioid sensitivity, but amplified opioid-evoked psychomotor sensitization following chronic fentanyl exposure. These results establish VGF as a modulator of nucleus accumbens synaptic and drug-evoked plasticity. Uncovering the impact of VGF on nucleus accumbens plasticity following exogenous opioid exposure may lead to novel therapeutic targets to treat opioid use disorders. SIGNIFICANCE STATEMENTThe opioid crisis has continued to have a devastating impact, and understanding the basic mechanisms underlying opioid use disorder may facilitate the discovery of new therapeutic targets. Neuropeptide signaling in the nucleus accumbens may be a potential site for intervention given the state-dependent recruitment of neuropeptides in reward circuitry. The neuropeptide precursor VGF has never been studied within the context of drug-evoked plasticity and behavior, despite its role in both adaptive and maladaptive plasticity, and evidence that drug exposure modulates its expression. Our findings show that VGF may be a novel modulator of NAc synaptic and opioid-evoked plasticity, building our understanding of the mechanisms responsible for drug-evoked adaptations and identifying VGF as an interesting potential target for future investigation.

neuroscience↗

bioRxiv2025

Chronic alcohol drinking delays recovery from capsaicin- and nerve injury-induced hypersensitivity in mice

Chronic pain and alcohol use disorder (AUD) are major health concerns that significantly impair quality of life. Persistent pain is common in individuals with alcohol dependence, and alcohol is commonly used by chronic pain patients for self-medication. The neural mechanisms linking these conditions remain unclear. We hypothesized that chronic alcohol exposure induces hypersensitivity in multiple modalities and increases the duration of recovery in acute and persistent pain models. Using the two-bottle free-choice alcohol consumption paradigm in adult mice, alcohol-induced hypersensitivity (AIH), indicated by reduced mechanical withdrawal thresholds, developed after 4-6 weeks of alcohol consumption compared to age- and sex-matched water-consuming controls. Alcohol-consuming female mice, but not male mice, developed cold hypersensitivity after AIH emerged. To assess the impact of chronic alcohol consumption on acute and persistent pain, we used intraplantar capsaicin and sciatic nerve crush models, respectively. In the capsaicin model, water-treated, but not alcohol-treated, mice recovered from hypersensitivity by 24 hours post-injection. In the sciatic nerve crush model, alcohol-consuming mice exhibited slower recovery of mechanical withdrawal thresholds compared to water-consuming controls. While mechanical hypersensitivity in water-consuming mice returned to pre-surgical thresholds by 3-4 weeks post-surgery, recovery in alcohol-consuming mice was both delayed and partial. Surgical intervention did not impact alcohol intake. Overall, our results suggest that chronic voluntary alcohol consumption facilitates the transition to chronic pain by prolonging hypersensitivity and delaying recovery from injuries. HighlightsO_LIMagnitude of alcohol-induced mechanical hypersensitivity is similar across sex C_LIO_LIFemales, but not males, develop alcohol-induced cold sensitivity C_LIO_LIChronic alcohol prolongs acute inflammatory pain C_LIO_LIChronic alcohol prolongs nerve-injury induced neuropathic pain C_LI

pharmacology and toxicology↗

bioRxiv2021

Targeting the nociceptive somatosensory system with AAV9 and AAV2retro viral vectors

Adeno-associated viral (AAV) vectors allow for site-specific and time-dependent genetic manipulation of neurons. However, for successful implementation of AAV vectors, major consideration must be given to the selection of viral serotype and route of delivery for efficient gene transfer into the cell type being investigated. Here we compare the transduction pattern of neurons in the somatosensory system following injection of AAV9 or AAV2retro in the parabrachial complex of the midbrain, the spinal cord dorsal horn, the intrathecal space, and the colon. Transduction was evaluated based on Cre-dependent expression of tdTomato in transgenic reporter mice, following delivery of AAV9 or AAV2retro carrying identical constructs that drive the expression of Cre/GFP. The pattern of distribution of tdTomato expression indicated notable differences in the access of the two AAV serotypes to primary afferent neurons via peripheral delivery in the colon and to spinal projections neurons via intracranial delivery within the parabrachial complex. Additionally, our results highlight the superior sensitivity of detection of neuronal transduction based on reporter expression relative to expression of viral products.

neuroscience↗