- |||||||||| aripiprazole / Generic mfg., methamphetamine / Generic mfg.
Establishment of the new mice model of circadian rhythm sleep-wake disorder (CRSWD) and search for its treatment (MCP Hall A) - Aug 22, 2024 - Abstract #Neuroscience2024Neuroscience_6257;
Furthermore, we found that administration of aripiprazole to mice model of jet lag showed advancing effects on the waking time. Our results may provide a stepping stone to understanding the pathogenesis of CRSWD with internal desynchronization and suggest that aripiprazole target modification of sleep-wake rhythms rather than circadian rhythms.
- |||||||||| fluoxetine / Generic mfg.
Red Blood Cell Membrane Camouflaging Nanodrugs Penetrate Blood-Brain Barrier for Enhanced Depression Therapy (MCP Hall A) - Aug 22, 2024 - Abstract #Neuroscience2024Neuroscience_6213;
In summary, for the first time, we have demonstrated the therapeutic effect of a fluoxetine-loaded RBC delivery system for enhanced depression therapy. Compared with free fluoxetine, this biomimetic nanocarrier can improve the therapeutic efficiency of antidepressant drugs and greatly shorten the therapy time for depression, which has great potential for clinical application in the future.
- |||||||||| clozapine / Generic mfg.
Chronic activation and inhibition of ventral segmental area melanocortin-3 receptor neurons (MCP Hall A) - Aug 22, 2024 - Abstract #Neuroscience2024Neuroscience_6161;
Following baseline measurement of food intake and body weight, mice were treated with clozapine N-oxide (CNO) chronically in their drinking water for eight days...These findings underscore the intricate interplay of MC3R signaling in the VTA, regulating feeding behaviors and body weight. Further exploration will delve into how VTA MC3R neurons activity control food intake and body weight, particularly on high-fat diets and in reward-based feeding paradigms.
- |||||||||| bupropion / Generic mfg., escitalopram / Generic mfg.
Reversal learning under 2-week bupropion or escitalopram treatment in mice (MCP Hall A) - Aug 22, 2024 - Abstract #Neuroscience2024Neuroscience_6108;
Further exploration will delve into how VTA MC3R neurons activity control food intake and body weight, particularly on high-fat diets and in reward-based feeding paradigms. Reversal learning was less efficient in both AD groups compared to the PLA group, as indicated by the increased number of trials needed for a reversal (Kruskal-Wallis test H=18.18, p<0.001; PLA mean ?=19, SD=3.5; ESC ?=27, SD=10.2, Cohen
- |||||||||| haloperidol / Generic mfg., clozapine / Generic mfg.
Prenatal stress modifies social behavior and the transcription of NMDA receptors. (MCP Hall A) - Aug 22, 2024 - Abstract #Neuroscience2024Neuroscience_5998;
As schizophrenia also has been associated with social withdrawal, increased GRIN2 expression in the hippocampus, and reduced GRIN2A/GRIN2B expression ratios in the hippocampus. These findings suggest that PRS in mice may have construct validity as a preclinical model for antipsychotic drug development.
- |||||||||| haloperidol / Generic mfg.
Basal ganglia output control of caudal PPN (MCP Hall A) - Aug 22, 2024 - Abstract #Neuroscience2024Neuroscience_5797;
We performed injections of the dopamine D2 receptor antagonist haloperidol to induce an acute PD-like hypokinetic state...In summary, cPPN-projecting neurons are a locomotor-promoting subpopulation of the STN, which might be a suitable target for alleviating locomotor dysfunctions in PD. In ongoing work, we are investigating the anatomical organization of cPPN-projecting STN neurons.
- |||||||||| Botox (onabotulinumtoxin A) / GSK, AbbVie, Healis Therap
Assessing motor unit activity during the evoked H-reflex in healthy individuals (MCP Hall A) - Aug 22, 2024 - Abstract #Neuroscience2024Neuroscience_5548;
These results provide an early feasibility demonstration of reliably extracting motor unit firings during the M wave and the H-reflex, despite the expected high degree of synchronization of motor unit firing. Future work will examine the utility of motor units in the context of H-reflex conditioning, including using motor units as a tool to measure M wave and H-reflex responses, investigate the mechanisms of HROC, and serve as a potential biomarker for predicting responsiveness to conditioning.
- |||||||||| clozapine / Generic mfg.
Investigating a possible role for the cerebellar interposed nucleus in habit behavior (MCP Hall A) - Aug 22, 2024 - Abstract #Neuroscience2024Neuroscience_5460;
The time taken to learn the task in IP-suppressed rats was not different from that in control rats. Furthermore, in a devaluation test after habit formation, there was no difference in responding between the control group and the IP-suppressed group.These results indicate that IP may not contribute to behavioral learning and habit formation in the discriminative stimulus task, although this conclusion should be considered tentative because we have not yet verified the effectiveness of DREADD inhibition of IP.
- |||||||||| clozapine / Generic mfg.
Social memory and interactive behaviors are sex-dependent and modulated by the cerebellum in mice (MCP Hall A) - Aug 22, 2024 - Abstract #Neuroscience2024Neuroscience_5459;
Mice received either clozapine-N-oxide (CNO, 1 mg/kg) or vehicle (0.9% saline) prior to testing in a within experimental design...However, untreated male mice were more inclined to investigate the novel conspecific during the social memory component, while cerebellar modulation led male mice to spend more time with the familiar conspecific. Examining the naturalistic behaviors of mice with machine learning can aid in uncovering the role of sex and the cerebellum on social behavior.
- |||||||||| clozapine / Generic mfg.
Aging and Autism: Modulation of the cerebellar nuclei during critical periods of development to assess social changes with age in mice (MCP Hall A) - Aug 22, 2024 - Abstract #Neuroscience2024Neuroscience_5458;
The CN-VTA pathway was inhibited with an inert ligand, clozapine-N-oxide (CNO), during postnatal days 21-35 (P21-35), followed by a washout period (5 days)...These results suggest that aging and reductions in neural complexity contribute to cognitive decline and future experiments will reveal aging and CN impacts on social changes in aging. This will be important in understanding how social behavior can be a key factor for early detection of cognitive deficits.
- |||||||||| clozapine / Generic mfg.
Amelioration of social behavior and alteration of cortical neural activity markers following adolescent cerebellar nuclei manipulation in mice (MCP Hall A) - Aug 22, 2024 - Abstract #Neuroscience2024Neuroscience_5457;
Males (n=20) and females (n=17) were exposed to the DREADD receptor ligand, clozapine-N-oxide (CNO; 10 mg/kg), in drinking water from postnatal day (PND) 21-35...These results suggest an early-life CN manipulation can impact adolescent social preference, potentially through changes in CN-VTA activity and/or distal cortical regions. These findings can guide clinical applications targeting development in individuals with neurodevelopmental disorders, such as ASD.
- |||||||||| clozapine / Generic mfg.
Silencing the caudal Nucleus of the Solitary Tract and the Postinspiratory Complex to unravel swallow and breathing neurocircuitry (MCP Hall A) - Aug 22, 2024 - Abstract #Neuroscience2024Neuroscience_5288;
Twenty-one days after injection, using our freely breathing urethane anesthetized mouse model, swallows were stimulated by 1) injection of water into the oral cavity and/or 2) optogenetic stimulation of PiCo neurons; before and after administration of DREADD activator, clozapine-N-oxide (CNO)...Silencing the cNTS resulted in an inability to evoke swallows either by water stimulation or optogenetic stimulation. We confirm that PiCo is important for postinspiration, normal swallow production, swallow-breathing coordination, and relies on direct feedback from the cNTS to trigger swallow production.
- |||||||||| haloperidol / Generic mfg.
Lack of m6A mRNA methylation blunts neuronal responses to environmental challenges, impairs learning, and reveals the opposing and cooperative roles of striatal D1 and D2 neurons (MCP Hall A) - Aug 22, 2024 - Abstract #Neuroscience2024Neuroscience_5259;
Furthermore, Mettl14 deletion in D1 MSNs impaired motor learning and blunted changes in neuronal activity during motor learning, whereas Mettl14 deletion in D2 MSNs blunted changes in neuronal activity during haloperidol-induced catalepsy and abolished sensitization of catalepsy...Our discovery demonstrated the role of a specific gene, by maintaining the normal neuronal activities, in regulating learning and environmental adaptation in a cell type specific manner. This study represents a good example in which knocking out the same gene in D1-MSNs vs D2-MSNs resulted in opposite behavioral phenotypes, and clearly demonstrated D1 MSN-dependent learning vs D2 MSN-dependent learning.
- |||||||||| clozapine / Generic mfg.
Immature olfactory sensory neurons provide complementary odor information (MCP Hall A) - Aug 22, 2024 - Abstract #Neuroscience2024Neuroscience_4821;
To test this hypothesis, we employed G?8-tTA;tetO-hM4Di transgenic mice to chemogenetically silence immature OSNs via clozapine N-oxide (CNO) mediated activation of the inhibitory DREADD hM4Di...Here we see that silencing immature OSNs reduces odor-evoked calcium responses in the OB to a variety of odorants. Together, these experiments suggest that immature OSNs provide information complementary to that provided by mature OSN activity, thus suggesting that immature OSNs make an important contribution to odor processing in the healthy OB.
- |||||||||| Turalio (pexidartinib) / Daiichi Sankyo
Microglia depletion blocks the induction of pain behaviors by chemogenetic activation of amygdala CRF neurons (MCP Hall A) - Aug 22, 2024 - Abstract #Neuroscience2024Neuroscience_3982;
Chemogenetic activation of amygdala CeA-CRF neurons with clozapine-N-oxide (CNO, 1.0 mg/kg, i.p. 7 days) induced long-lasting pain-like behaviors and microglia activation in CRF-cre rats, which was blocked by an inhibitor of microglia colony-stimulating factor-1 receptor CSF1R (PLX3397, oral gavage, 30 mg/kg, 7 days).The data suggest that microglia activation is downstream of CRF signaling in the amygdala, providing evidence for an important role of the amygdala CRF system in neuroimmune pain mechanisms in the brain. Keyword (s): CRF CeA, chemogenetics, amygdala, pain Support Contributed By: NIH Grants NS038261, NS106902, NS109255
- |||||||||| Turalio (pexidartinib) / Daiichi Sankyo
Spinal Microglia Maintain Multiple Sclerosis-Associated Neuropathic Pain (MCP Hall A) - Aug 22, 2024 - Abstract #Neuroscience2024Neuroscience_3806;
Keyword (s): CRF CeA, chemogenetics, amygdala, pain Support Contributed By: NIH Grants NS038261, NS106902, NS109255 Next, they received either: 1) Local microglial depletion at the spinal cord or brain with injection of liposome encapsulated clodronate (LEC) by the intrathecal (50
- |||||||||| clozapine / Generic mfg.
Central terminals of primary afferents as synchronizing element in spinal cord circuits. (MCP Hall A) - Aug 22, 2024 - Abstract #Neuroscience2024Neuroscience_3789;
Activation of hM4Di-DREADD with clozapine N-oxide led to a reduction in the frequency of sDRP and the firing of dorsal horn neurons, with a concomitant loss of coordinated activity...These results show that the ability of primary afferents to transmit information can be strongly regulated by acting at their central terminals inside the cord. Primary afferents terminals work as an essential component in maintaining coordination in the spontaneous activity of spinal circuits, contributing to adjust their excitability Financial support MICINN PID2021-126330OB-I00.
- |||||||||| tramadol hydrochloride / Generic mfg., haloperidol / Generic mfg.
The sigma-one receptor antagonist potentiates the opioid receptors: antinociceptive synergism in rats (MCP Hall A; Virtually Only) - Aug 22, 2024 - Abstract #Neuroscience2024Neuroscience_3713;
Primary afferents terminals work as an essential component in maintaining coordination in the spontaneous activity of spinal circuits, contributing to adjust their excitability Financial support MICINN PID2021-126330OB-I00. The antinociceptive effects of the combination of haloperidol/tramadol (ED50 =0.153
- |||||||||| sumatriptan succinate / Generic mfg.
Abhd6 partially reversed medication overuse headache induced allodynia induced by sumatriptan (MCP Hall A) - Aug 22, 2024 - Abstract #Neuroscience2024Neuroscience_3665;
In rats with headache like behaviors, those that received the ABHD6 inhibitor had periorbital allodynia thresholds statistically higher than those receiving vehicle, suggesting that targeting ABHD6 for MOH attenuation is a potential strategy. Targeting ABHD6 with the inhibitor KT-182 mitigated periorbital allodynia in sumatriptan induced MOH animals, indicating a potential intervention for the reversal of MOH.Late-Breaker Justification: Data collection was still underway during the initial timeframe o fabstract submission; therefore, results could not be completed until now.This study is supported by NIH R01-NS126752-01A1
- |||||||||| sumatriptan succinate / Generic mfg.
Miniscope-based in vivo blood vessel imaging enables a novel assay for testing migraine therapeutic candidates (MCP Hall A) - Aug 22, 2024 - Abstract #Neuroscience2024Neuroscience_3655;
Ongoing efforts include employing these methods to investigate additional potential mechanisms and therapeutic targets implicated in migraine, such as CGRP, VIP or, for instance, assessing whether migraine abortives like Sumatriptan prevents PACAP-induced vasodilation. Our findings may be beneficial for future perspectives on potential migraine therapeutics.
- |||||||||| morphine sulphate / Generic mfg., sumatriptan succinate / Generic mfg.
Comparison of rat models of vascular headache and trigeminal sensitization in male and female rats (MCP Hall A) - Aug 22, 2024 - Abstract #Neuroscience2024Neuroscience_3650;
The data demonstrate that facial allodynia produced in rat models of vascular headache and trigeminal sensitization is generally more robust in female rats compared to male rats. Additionally, certain classes of analgesic compounds, including delta opioid agonists, are more effective in preventing the development of facial allodynia in male rats compared to female rats.
- |||||||||| amitriptyline / Generic mfg., naproxen / Generic mfg.
Does spreading depression rewire cortical pain networks? (MCP Hall A) - Aug 22, 2024 - Abstract #Neuroscience2024Neuroscience_3647;
Additionally, certain classes of analgesic compounds, including delta opioid agonists, are more effective in preventing the development of facial allodynia in male rats compared to female rats. C57BL6-ChR2 mice received i.p. amitriptyline or normal saline for 4
- |||||||||| haloperidol / Generic mfg.
The role of nigrostriatal dopamine in hallucination-like percepts in mice (MCP Hall A) - Aug 22, 2024 - Abstract #Neuroscience2024Neuroscience_3560;
Importantly, this effect was blocked by pre-treatment with the antipsychotic drug haloperidol...Based on the literature, we hypothesize that excess dopamine in the TS induces HALIPs, whereas excess dopamine in the DMS drives more motor-based deficits associated with schizophrenia. Taken together, our results present a novel understanding for how excess dopamine, as reported in schizophrenia, causes hallucinations and provides a gateway for developing novel therapeutic approaches for treating psychosis, based on modulation of specific dopaminergic pathways.
- |||||||||| desipramine / Generic mfg.
Ultrasoft neural probe for deep brain stimulation to treat Parkinson's disease (MCP Hall A) - Aug 22, 2024 - Abstract #Neuroscience2024Neuroscience_3164;
These properties potentially enable more effective and longer-lasting neuromodulation, as demonstrated in a rat model of Parkinson's disease.Method The PD model was established by administering desipramine intraperitoneally, followed by injecting 6-OHDA into the Substantia Nigra (AP: -5.0mm, ML: +2.0mm, DV: -7.5mm)...Using a PD animal model, it was shown that DBS with liquid metal electrodes effectively addresses motor symptoms of the disease. Liquid metal electrodes thus represent a promising alternative in the advancement of treatment technologies for Parkinson's disease.
- |||||||||| haloperidol / Generic mfg.
Contribution of the Sigma 1 receptor as a neuroprotector against damage in a preclinical model of chronic kidney disease (MCP Hall A) - Aug 22, 2024 - Abstract #Neuroscience2024Neuroscience_3152;
There is an important need to develop pharmacological strategies focused on reducing chronic damage in patients with neurological disorders caused by CKD, which is why this project seeks to clarify how the S1R influences in neuroprotection in a preclinical model of chronic kidney disease.For this, a model of chronic kidney damage was carried out through unilateral ureteral obstruction (UUO) in female and male C57BL/6 mice, which were divided into 5 groups, the Sham group, the group with UUO and physiological saline solution, the group of OUU and PRE 084, the group of OUU (0.5 mg/Kg) and NE100 (0.5 mg/Kg) and the group of OUU and haloperidol (2 mg/Kg), and each of these groups, in turn divided into subgroup of females and males, were sacrificed 21 days after surgery and different organs were taken (kidney, heart, brain)...It remains to be done. various techniques that make it easier for us to observe damage to the nervous system, such as astrocyte reactivity in different areas of the brain, as well as markers of cell death to identify if there is any difference between the various study groups, as well as sexual differences, as observed with the kidney and the heart.
- |||||||||| memantine / Generic mfg.
Diversity of CA1 pyramidal plasticity modulated by fast-spiking PV interneurons in an AD mouse model (MCP Hall A) - Aug 22, 2024 - Abstract #Neuroscience2024Neuroscience_2385;
Intriguingly, the administration of memantine in acute hippocampal slices rescued the diminished LTP in superficial CA1PNs of 5xFAD mice compared to wild-type mice...Modulating electrophysiological properties and NMDAR functions in PVBCs may improve cognitive behaviors by retuning the working mode of the PVBC-CA1PNs microcircuit in the AD brain. The study may pave a promising path to a combination of drug therapies and non-invasive administration for AD.
- |||||||||| clozapine / Generic mfg.
Long-term Electrical Motor Cortex Stimulation Alleviates Motor Dysfunction in a Mouse Model of Parkinson (MCP Hall A; Virtually Only) - Aug 22, 2024 - Abstract #Neuroscience2024Neuroscience_2158;
Following inhibition of the hyperdirect pathway with Clozapine N-oxide, mice subjected to long-term MCS showed significantly less behavioral improvement in the cylinder test (p = 0.039) and pole test (p = 0.041) than those in the MCS treatment group...Furthermore, the activation of the hyperdirect pathway contributes to the long-term protective effects observed with MCS. This study provides evidence that MCS is an efficacious therapeutic approach for motor dysfunctions in PD, offering insights into the mechanisms underlying its treatment.
- |||||||||| fluoxetine / Generic mfg.
Exploring the antidepressant potential of Delonix regia extracts: Insights into mitigating depression and oxidative stress (MCP Hall A) - Aug 22, 2024 - Abstract #Neuroscience2024Neuroscience_1592;
Fluoxetine, a benchmark pharmaceutical agent, served as a reference standard...The findings suggest Delonix regia extracts (200, 400 mg/kg) can serve as a potential antidepressant both individually and as adjunctive agents in the treatment of depression. Inhibition of the inflammatory mediators during stress procedures or any other potential physiological and biochemical mechanisms may be involved in its antidepressant effect.
- |||||||||| haloperidol / Generic mfg.
A2a r antagonist attenuated the soce mediated calcium homeostasis and impaired mitochondrial membrane potential in 6-ohda induced parkinson (MCP Hall A; Virtually Only) - Aug 22, 2024 - Abstract #Neuroscience2024Neuroscience_1452;
Previously our lab synthesized and validated various A2A R antagonist (Mishra et al, 2010;2013) in haloperidol induced model in which BBPT possessed numerous pharmacological benefits...Also, BBPT significantly improved ROS level to protect the PMDN cells from the 6-OHDA induced neurodegeneration. Our findings provide the first evidence on the ability of A2AR antagonist (BBPT) to maintain SOCE mediated Ca2+ homeostasis, inhibited PM-ER stress and protect the ??(m) from 6-OHDA induced neurodegeneration in PMDN cells.
- |||||||||| chlorpromazine / Generic mfg.
Trehalose-mediated lysosomal enhancement: a promising strategy for mitigating neurotoxicity in acute ischemic brain injury (MCP Hall A) - Aug 22, 2024 - Abstract #Neuroscience2024Neuroscience_1263;
To further assess its neuroprotective potential, trehalose was administered intraperitoneally at a dose of 2 g/kg daily four times and additionally provided in drinking water (3% w/v) for a week before permanent middle cerebral artery occlusion surgery, resulting in a significant reduction in infarct size. Our findings underscore the potential of lysosomal upregulation mechanisms as crucial protective mechanisms not only in neurodegenerative diseases but also in acute brain injuries.
- |||||||||| clozapine / Generic mfg.
Retinal regulation of Locus coeruleus: a chemogenetic approach to treat neurodegenerative disorders (MCP Hall A) - Aug 22, 2024 - Abstract #Neuroscience2024Neuroscience_1129;
Learning and memory deficits in Alzheimer disease, associated with dysregulation of the noradrenergic LC, can be attenuated by PRAM-induced activation of LC. The PRAM pathway is a novel and relatively non-invasive approach to treating AD and other neuropsychiatric disorders linked to LC function.
- |||||||||| Belviq (lorcaserin) / Eisai
5ht2c agonism as a treatment for age-related neural hypoexcitability and weakness (MCP Hall A) - Aug 22, 2024 - Abstract #Neuroscience2024Neuroscience_790;
To explore this hypothesis, we began by evaluating the effect of a single dose of lorcaserin, a highly selective 5HT2c agonist, on neural excitability in 26-month-old male and female mice...Overall, our data suggests that 5HT2c agonism is a promising therapeutic approach for treating age-related neural hypoexcitability and weakness. Importantly, 5HT2c agonism may be an effective strategy for treating weakness and physical frailty in the older adults, greatly improving quality of life and healthspan.
- |||||||||| clozapine / Generic mfg.
Novel insights into astrocyte-neuron interactions in nociceptive processing at the spinal level (MCP Hall A) - Aug 22, 2024 - Abstract #Neuroscience2024Neuroscience_715;
Gq-DREADDs or a control construct were delivered to the lumbar spinal cord of male rats using a viral approach, and selectively activated using clozapine-N-oxide (CNO)...Our discoveries imply that astrocytes might exert diverse effects on synaptic transmission contingent upon the activating stimulus, thus underscoring their pivotal role in maintaining the equilibrium between inhibition and excitation within nociceptive circuits. Through further experiments, including an examination of the astrocytic secretome, we seek to enhance our comprehension of the dynamic interplay between astrocytes and neurons in the processing of pain.
- |||||||||| chlorpromazine / Generic mfg., clozapine / Generic mfg.
Probes for the Heterogeneity of Muscimol Binding Sites in Rat Brain (MCP Hall A) - Aug 22, 2024 - Abstract #Neuroscience2024Neuroscience_689;
Our experimental findings are supported by docking analysis, designed to find structural correlates of the observed diversity of muscimol sites that are present in the samples from brain tissue and recombinantly expressed GABAA receptor subunit combinations.These findings indicate that 3H-muscimol binding sites in rat brain are more heterogenous than previously thought, with different populations of receptors, which are CPZ, LOX or CLZ sensitive or insensitive. These binding sites show a varying distribution in different rat brain regions.
- |||||||||| dizocilpine (MK801) / Merck (MSD)
Membrane to channel path of NMDA receptor inhibition by intracellularly applied MK-801 (MCP Hall A) - Aug 22, 2024 - Abstract #Neuroscience2024Neuroscience_580;
Finally, we developed a kinetic model of GluN1/2A receptor inhibition to determine whether properties of inhibition by iMK-801 are consistent with MCI. The data from these investigations support our hypothesis that inhibition by iMK-801 acts through MCI and will deepen our understanding of an important class of drug.
- |||||||||| aripiprazole / Generic mfg., amitriptyline / Generic mfg., haloperidol / Generic mfg.
Optimization of a multiplexed, cell-based assay of neuronal function (MCP Hall A) - Aug 22, 2024 - Abstract #Neuroscience2024Neuroscience_494;
In contrast, dosing with the inhibitory or anti-psychotic compounds led to decreases in all three neural network characteristics. In total, this study shows that the Maestro Pro is a valuable tool for optimizing in vitro neural models and detecting electrophysiological changes from neuroactive compounds.
|
