Neuroscience
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The neuropeptide somatostatin is widely distributed in the CNS and is believed to play a role as a neurotransmitter or a neuromodulator. Somatostatin mediates its actions by the binding of the peptide to high affinity membrane receptors. The genes for five somatostatin receptor types have been cloned recently and Northern blotting and in situ hybridization studies have shown that the transcripts of all five types are expressed in the CNS. ⋯ Cells and processes were labelled in a number of areas, including the basolateral amygdala, the locus coeruleus, the endopiriform nucleus, the deep layers of the cerebral cortex, the subiculum, the claustrum, the habenula, the interpenduncular nucleus, the hippocampus and the central grey. In the spinal cord, the substantia gelatinosa showed strongly-labelled cell bodies and their processes. This study provides an improved understanding of the distribution of the sst2(a) receptor in rat brain.
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To localize glycinergic cell bodies and fibers in the rat brain, we developed a sensitive immunohistochemical method combining the use of specific glycine antibodies (Campistron G. et al. (1986) Brain Res. 376, 400-405; Wenthold R. J. et al. (1987) Neuroscience 22, 897-912) with the streptavidin-horseradish peroxidase technique and 3,3'-diaminobenzidine.4HCl-nickel intensification. We confirmed the presence of numerous glycine-immunoreactive cell bodies and fibers in the cochlear nuclei, superior olivary complex, nucleus of the trapezoid body, cerebellar cortex, deep cerebellar nuclei and area postrema. ⋯ We also provide the first evidence in rats for a very large number of fibers in the trigeminal, facial, ambiguous and hypoglossal motor nuclei, all nuclei of the medullary and pontine reticular formation, and the raphe and trigeminal sensory nuclei. We further revealed the presence of a substantial number of fibers in regions where glycine was not considered as a main inhibitory neurotransmitter, such as the pontine nuclei, the periaqueductal gray, the mesencephalic reticular formation, the anterior pretectal nucleus, the intralaminar thalamic nuclei, the zona incerta, the fields of Forel, the parvocellular parts of the paraventricular nucleus, the posterior hypothalamic areas, the anterior hypothalamic area, and the lateral and medial preoptic areas. These results indicate that, in contrast to previous statements, glycine may be an essential inhibitory neurotransmitter not only in the lower brainstem and spinal cord, but also in the upper brainstem and the forebrain.
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The heptadecapeptide orphanin FQ has recently been shown to be the endogenous agonist for the orphan opioid-like receptor, LC132. The molecular evidence that LC132 and orphanin FQ are evolutionarily related to other opioid receptors and their ligands suggests that these proteins may also play a role in modulating opiate actions. ⋯ In addition to its antagonism of endogenous opioid antinociception, orphanin FQ dose-dependently (2.5-25 nmol) reverses systemic morphine antinociception (5 mg/kg, s.c.). Based on these data, we propose that orphanin FQ is a functional anti-opioid peptide.
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Autotomy in experimental animals following peripheral nerve section has been interpreted as a sign of pain corresponding to the chronic pain observed in patients with extensive nerve lesions. Such pain may be alleviated by spinal cord stimulation. In the present study, the effect of such stimulation, via chronically implanted electrodes, on autotomy behavior following sciatic nerve section was assessed in the rat. ⋯ It seems that spinal cord stimulation, albeit applied only once daily and during a limited time period, can protect the spinal cord from developing the state of hyperexcitability believed to be the major cause of autotomy behavior. Peripheral mechanisms may also play a role by the antidromic activity evoked by the stimulation in the sectioned peripheral nerve. This study shows that spinal cord stimulation, which is a commonly employed method for treating chronic neurogenic pain, may have long-lasting effects on plasticity changes in the spinal cord following peripheral nerve injury, even when the stimulation is applied for short periods of time.
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Cloning studies have identified a novel seven transmembrane receptor displaying high sequence homology to the three classical opioid receptors (mu, delta and kappa). This receptor is widely distributed throughout the CNS. 1 Recently, an endogenous ligand for this receptor was isolated (termed either "orphanin FQ" or "nociceptin") and identified as a heptadecapeptide showing sequence homology with the endogenous opioids. Surprisingly, in contrast to known opioids, orphanin FQ displays hyperalgesic rather than analgesic properties. ⋯ These preliminary data suggest that orphanin FQ systems may act in an opposing manner to the previously well-described enkephalin and endorphin systems. Since numerous studies have implicated activation of the mesolimbic dopamine pathway to be central to the rewarding actions of opiates such as morphine and heroin, as well as several other abused drugs, and also to mediate the hyperlocomotory action of such drugs, we sought to determine the effect of orphanin FQ on this pathway. In accordance with the inhibitory effect of this peptide on locomotor activity, we now report that orphanin FQ suppresses dopamine release in the nucleus accumbens in a dose-dependent manner, providing the first neurochemical evidence for a modulatory role of this recently described peptide in the CNS.