Norwoodmose1944

A role of striatal muscarinic cholinergic neurons is suggested since co-infusion of SP with atropine (10 μM), but not the nicotinic receptor mecamylamine (10 μM), blocked antinociception. The current study suggests that activation of striatal muscarinic receptors through NK1 receptors could be a novel approach to managing chronic pain.Bone morphogenetic protein (BMP) signaling in the hippocampus regulates psychiatric behaviors and hippocampal neurogenesis in non-stress conditions; however, stress-induced changes in hippocampal BMP signaling have not yet been reported. Therefore, we sought to examine whether psychosocial stress, which induces psychiatric symptoms, affects hippocampal BMP signaling. A total of 32 male Sprague-Dawley rats were exposed to a psychosocial stress using a Resident/Intruder paradigm for ten consecutive days. Subsequently, rats were subjected to a battery of behavioral tests (novelty-suppressed feeding test, sucrose preference test, and forced swimming test) for the evaluation of adult neurogenesis and activity of BMP signaling in the dorsal and ventral hippocampus. Repeated social defeat promoted anxiety-like behaviors, but neither anhedonia nor behavioral despair. Socially defeated rats exhibited an increase in the number of Ki-67-positive cells, decrease in the number of doublecortin (DCX)-positive cells, and decrease only in the dorsal hippocampus of the ratio of DCX-positive to Ki-67-positive cells, a proxy for newly-born cell maturation speed and survival. In contrast, no differences were observed in the number of 5-Bromo-2'-deoxyuridine (BrdU)-positive cells, indicating survival of newly-born cells both in the dorsal and ventral hippocampus. Furthermore, psychosocial stress significantly increased the BMP-4 and phosphorylated Smad1/5/9 expression levels specifically in the dorsal hippocampus. Our findings suggest that repeated psychosocial stress activates BMP signaling and differently affects cell proliferation and neurogenesis exclusively in the dorsal hippocampus, potentially exacerbating anxiety-related symptoms. Targeting BMP signaling is a potential therapeutic strategy for psychiatric disorders.Repetitive behaviors (e.g., stereotypic movements, compulsions, rituals) are common features of a number of neurodevelopmental disorders. Clinical and animal model studies point to the importance of cortical-basal ganglia circuitry in the mediation of repetitive behaviors. In the current study, we tested whether a drug cocktail (dopamine D2 receptor antagonist + adenosine A2A receptor agonist + glutamate mGlu5 positive allosteric modulator) designed to activate the indirect basal ganglia pathway would reduce repetitive behavior in C58 mice after both acute and sub-chronic administration. In addition, we hypothesized that sub-chronic administration (i.e. 7 days of twice-daily injections) would increase the functional activation of the subthalamic nucleus (STN), a key node of the indirect pathway. Functional activation of STN was indexed by dendritic spine density, analysis of GABA, glutamate, and synaptic plasticity genes, and cytochrome oxidase activity. The drug cocktail used significantly reduced repetitive motor behavior in C58 mice after one night as well as seven nights of twice-nightly injections. These effects did not reflect generalized motor behavior suppression as non-repetitive motor behaviors such as grooming, digging and eating were not reduced relative to vehicle. Sub-chronic drug treatment targeting striatopallidal neurons resulted in significant changes in the STN, including a four-fold increase in brain-derived neurotrophic factor (BDNF) mRNA expression as well as a significant increase in dendritic spine density. E1 Activating inhibitor The present findings are consistent with, and extend, our prior work linking decreased functioning of the indirect basal ganglia pathway to expression of repetitive motor behavior in C58 mice and suggest novel therapeutic targets.Binocular rivalry (BR) occurs when monocular images are presented simultaneously to corresponding regions of the two eyes. Rather than forming a stable composite, perception alternates spontaneously between each monocular view. Over recent decades, considerable interest in examining BR in psychiatric populations has demonstrated clear differences in the dynamics of BR when compared to healthy populations. However, the available data with respect to rivalry rates in depression and anxiety are limited, and previous studies have shown inconsistent results. Also, depression and anxiety are highly comorbid and can be difficult to distinguish. Therefore, we aimed to investigate whether patients with depression and anxiety have abnormal rivalry rates and whether rivalry rates differ between these conditions. Thirty-five patients with major depressive disorder (MDD), 30 patients with generalized anxiety disorder (GAD), and 30 control participants matched on sex, age and education were recruited. Our results showed MDD participants had slower BR rates than controls and GAD, and controls were significantly slower than GAD. Our findings raise prospects that BR could be a promising behavioral tool to differentiate depressive and anxiety disorders.Autism spectrum disorders (ASDs) are highly prevalent childhood illnesses characterized by impairments in communication, social behavior, and repetitive behaviors. Studies have found aberrant synaptic plasticity and neuronal connectivity during the early stages of brain development and have suggested that these contribute to an increased risk for ASD. STEP is a protein tyrosine phosphatase that regulates synaptic plasticity and is implicated in several cognitive disorders. Here we test the hypothesis that STEP may contribute to some of the aberrant behaviors present in the VPA-induced mouse model of ASD. In utero VPA exposure of pregnant dams results in autistic-like behavior in the pups, which is associated with a significant increase in the STEP expression in the prefrontal cortex. The elevated STEP protein levels are correlated with increased dephosphorylation of STEP substrates GluN2B, Pyk2 and ERK, suggesting upregulated STEP activity. Moreover, pharmacological inhibition of STEP rescues the sociability, repetitive and abnormal anxiety phenotypes commonly associated with ASD.