Non-peptidic delta opioid receptor agonists are being evaluated for a wide range of clinical applications; however, the clinical utility of piperazinyl benzamide delta agonists such as SNC80 may be limited by convulsant activity. The purpose of the present study was to evaluate the electroencephalographic and convulsant activity produced by a high dose of 10 mg/kg SNC80 IM in rhesus monkeys. EEG and behavioral activity were examined in four adult male rhesus monkeys after IM administration of SNC80. Monkeys were seated in a standard primate restraint chair, and EEG activity was recorded using an array of 16 needle electrodes implanted subcutaneously in the scalp in a bipolar (scalp-to-scalp) montage in a longitudinal direction, with bilateral frontal, central, temporal, and occipital leads. Behavior was recorded using video monitoring equipment. Initially, all monkeys were tested with 10 mg/kg SNC80, which is a relatively high dose 3-10-fold greater than doses necessary to produce a variety of other behavioral effects. Behavioral convulsions and EEG seizures were observed in one of the four monkeys. In this monkey, neither behavioral convulsions nor EEG seizures were observed when a lower dose of 3.2 mg/kg was administered nine weeks later or when the same dose of 10 mg/kg SNC80 was administered one year later. These results suggest that IM administration of SNC80 is less potent in producing convulsant effects than in producing other, potentially useful behavioral effects (e.g. antinociception) in rhesus monkeys.
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http://dx.doi.org/10.1016/j.pbb.2006.09.012 | DOI Listing |
Alzheimers Dement
December 2024
Queen's University, Kingston, ON, Canada; D'OR Institute for Research and Education, Rio de Janeiro, Rio de Janeiro, Brazil.
Background: Physical exercise improves overall brain health, cognition, and stimulates the release of extracellular vesicles (EVs) in humans. Exercise upregulates irisin, a myokine derived from fibronectin type III domain-containing protein 5 (FNDC5) previously shown to mediate the beneficial actions of exercise on memory in mouse models of Alzheimer's disease (AD). Here, we investigated if physical exercise upregulates EVs.
View Article and Find Full Text PDFAlzheimers Dement
December 2024
Yale University, New Haven, CT, USA.
Background: Advances in Alzheimer's disease (AD) have revealed a novel fluid biomarker, tau phosphorylated at T217 (pT217-tau), in CSF and plasma, that predicts AD prior to cognitive deficits. Understanding the role of pT217-tau is important in assessing efficacy of novel treatments aimed at early-stage disease. However, it is unknown why pT217-tau is effective in predicting brain pathology, as little is known about early, soluble pT217-tau brain expression.
View Article and Find Full Text PDFNat Commun
January 2025
McGovern Institute for Brain Research, Massachusetts Institute of Technology, Cambridge, MA, USA.
A central tenet of cognitive neuroscience is that humans build an internal model of the external world and use mental simulation of the model to perform physical inferences. Decades of human experiments have shown that behaviors in many physical reasoning tasks are consistent with predictions from the mental simulation theory. However, evidence for the defining feature of mental simulation - that neural population dynamics reflect simulations of physical states in the environment - is limited.
View Article and Find Full Text PDFBone Res
January 2025
The Guangdong Provincial Key Laboratory of Brain Connectome and Behavior, CAS Key Laboratory of Brain Connectome and Manipulation, the Brain Cognition and Brain Disease Institute (BCBDI), Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences; Shenzhen-Hong Kong Institute of Brain Science-Shenzhen Fundamental Research Institutions, Shenzhen, China.
Osteoarthritis (OA) is a degenerative joint disease accompanied with the loss of cartilage and consequent nociceptive symptoms. Normal articular cartilage maintains at aneural state. Neuron guidance factor Semaphorin 3A (Sema3A) is a membrane-associated secreted protein with chemorepulsive properties for axons.
View Article and Find Full Text PDFFront Cell Infect Microbiol
January 2025
Department of Virology, Biomedical Primate Research Centre (BPRC), Rijswijk, Netherlands.
Infection of an adult rhesus macaque with SARS-CoV-2 led to viral RNAemia in nose, throat, and lungs. The animal also presented extended fecal shedding of viral genomic and subgenomic messenger RNA and replication-competent virus for more than 3 weeks after infection. Positron emission tomography revealed increased intestinal glucose metabolism which was histologically related to inflammation of the ileum.
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