Neuroscience
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The mu opioid receptor plays an important role in mediating the actions of morphine and morphine-like drugs. Receptor binding and a wide range of pharmacological studies have proposed several mu receptor subtypes, but only one mu opioid receptor (Oprm) gene has been isolated. Like the mouse and rat, the human Oprm gene undergoes alternative splicing. ⋯ Receptor binding assays established that these variants belonged to the mu opioid receptor family with limited differences in mu opioid ligand affinities and selectivity. However, adenylyl cyclase and [35S]GTPgammaS binding assays revealed major differences in both potency and efficacy among these variants. The dissociation between binding affinity, potency and efficacy for the opioids among these variants may provide insights into the wide range of opioid responses among these agents observed clinically and opens new avenues in designing selective drugs based upon their efficacy and potency rather simple binding affinity.
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The role of central serotonin 3 receptors on neural activities recorded from superficial laminae of trigeminal subnucleus caudalis/upper cervical spinal cord junction region was investigated using rats with (Complete Freund's Adjuvant day 7 group) or without (non-Complete Freund's Adjuvant group) persistent temporomandibular joint inflammation evoked by Complete Freund's Adjuvant for 7 days. We identified two types of units, Deep-wide dynamic range units and Skin-wide dynamic range units from extracellular recordings. Deep-wide dynamic range units have mechanoreceptive fields in the deep craniofacial tissues including masseter muscle but do not have cutaneous mechanoreceptive fields. ⋯ The role of central serotonin 3 receptors in trigeminal subnucleus caudalis/upper cervical spinal cord junction region was also tested by orofacial formalin test in Complete Freund's Adjuvant day 7 group. Intracisternal administration of tropisetron decreased the orofacial nocifensive behavior in the late phase evoked by the injection of formalin into the masseter muscle. These results suggest that central serotonin 3 receptors in trigeminal subnucleus caudalis/upper cervical spinal cord junction region are involved in mediating pronociceptive effects in both superficial and deep craniofacial tissues nociception during persistent temporomandibular joint inflammation.
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Comparative Study
Fos activation in hypothalamic neurons during cold or warm exposure: projections to periaqueductal gray matter.
The hypothalamus, especially the preoptic area, plays a crucial role in thermoregulation, and our previous studies showed that the periaqueductal gray matter is important for transmitting efferent signals to thermoregulatory effectors in rats. Neurons responsible for skin vasodilation are located in the lateral portion of the rostral periaqueductal gray matter, and neurons that mediate non-shivering thermogenesis are located in the ventrolateral part of the caudal periaqueductal gray matter. We investigated the distribution of neurons in the rat hypothalamus that are activated by exposure to neutral (26 degrees C), warm (33 degrees C), or cold (10 degrees C) ambient temperature and project to the rostral periaqueductal gray matter or caudal periaqueductal gray matter, by using the immunohistochemical analysis of Fos and a retrograde tracer, cholera toxin-b. ⋯ On the other hand, when cholera toxin-b was injected into the caudal periaqueductal gray matter, many double-labeled cells were seen in a cell group extending from the dorsomedial nucleus through the dorsal hypothalamic area in cold-exposed rats but few were seen in warm-exposed rats. These results suggest that the rostral periaqueductal gray matter receives input from the median preoptic nucleus neurons activated by warm exposure, and the caudal periaqueductal gray matter receives input from neurons in the dorsomedial nucleus/dorsal hypothalamic area region activated by cold exposure. These efferent pathways provide a substrate for thermoregulatory skin vasomotor response and non-shivering thermogenesis, respectively.
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Most drugs of abuse increase dopamine (DA) in the nucleus accumbens (NAc), and do so every time as a pharmacological response. Palatable food also releases accumbens-shell DA, but in naïve rats the effect can wane during a long meal and disappears with repetition. Under select dietary circumstances, sugar can have effects similar to a drug of abuse. ⋯ In the Daily Intermittent Sucrose group, the highest ACh levels (133%) occurred during the first sample after the sucrose meal ended. In summary, sucrose-dependent animals have a delayed ACh satiation response, drink more sucrose, and release more DA than sucrose- or binge-experienced, but non-dependent animals. These results suggest another neurochemical similarity between intermittent bingeing on sucrose and drugs of abuse: both can repeatedly increase extracellular DA in the NAc shell.
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Our previous studies have shown that intracerebral administration of endotoxin, lipopolysaccharide (LPS), induces selective white matter injury and hypomyelination in the neonatal rat brain and that the LPS-induced brain injury is associated with activation of microglia. To test the hypothesis that inhibition of microglial activation may protect against LPS-induced white matter injury, we examined roles of minocycline, a putative suppressor of microglial activation, on LPS-induced brain injury in the neonatal rat. A stereotactic intracerebral injection of LPS (1 mg/kg) was performed in postnatal day 5 Sprague-Dawley rats and control rats were injected with sterile saline. ⋯ The protective effect of minocycline was associated with suppressed microglial activation as indicated by the decreased number of activated microglial cells following LPS stimulation and with consequently decreased elevation of interleukin 1beta and tumor necrosis factor-alpha concentrations induced by LPS and a reduced number of inducible nitric oxide synthase expressing cells. Protection of minocycline was also linked with the reduction in LPS-induced oxidative stress, as indicated by 4-hydroxynonenal positive OLs. The overall results suggest that reduction in microglial activation may protect the neonatal brain from LPS-induced white matter injury and inhibition of microglial activation might be an effective approach for the therapeutic treatment of infection-induced white matter injury.