Neuroscience
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Human immunodeficiency virus (HIV) infection selectively targets the striatum, a region rich in opioid receptor-expressing neural cells, resulting in gliosis and neuronal losses. Opioids can be neuroprotective or can promote neurodegeneration. To determine whether opioids modify the response of neurons to human immunodeficiency virus type 1 (HIV-1) Tat protein-induced neurotoxicity, neural cell cultures from mouse striatum were initially characterized for mu and/or kappa opioid receptor immunoreactivity. ⋯ Neuronal losses were accompanied by chromatin condensation and pyknosis. Astrocyte viability was unaffected. These findings demonstrate that acute opioid exposure can exacerbate the neurodegenerative effect of HIV-1 Tat protein in striatal neurons, and infer a means by which opioids may hasten the progression of HIV-associated dementia.
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The opioid receptor-like 1 (ORL1) receptor shares a high degree of sequence homology with the classical mu-, delta- and kappa-opioid receptors and a functional mutual opposition between these receptors has been suggested. To further address this possible interaction we have used mu-, delta- and kappa-opioid receptor knockout mice to determine autoradiographically if there are any changes in the number or distribution of the ORL1 receptor, labelled with [(3)H]nociceptin, in the brains of mice deficient in each of the opioid receptors. An up-regulation of ORL1 expression was observed across all brain regions in delta-knockouts with cortical regions typically showing a 15-30% increase in binding that was most marked in heterozygous mice. ⋯ No significant alterations in ORL1 receptor expression were observed across brain regions in mu-receptor knockout mice and there were no qualitative differences in ORL1 receptor expression in any groups. These data suggest there are interactions between the ORL1 system and the classical opioid receptors and that the interactions are receptor-specific. The greater differences observed in heterozygous mice suggest that these interactions might be most relevant when there is only partial loss of receptor function.
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The present study investigated the modulatory actions of nociceptin/orphanin FQ on excitatory glutamatergic transmission in spinal dorsal horn. In transverse spinal cord slices with an attached dorsal root, mono- and polysynaptic A delta-fibre-evoked extracellular field potentials were recorded from superficial dorsal horn. ⋯ None of the actions of nociceptin/orphanin FQ was reversed by the non-specific opioid receptor antagonist naloxone, the N-methyl-D-aspartate receptor antagonist D-2-amino-5-phosphonovaleric acid or the peptide nocistatin. The bidirectional actions of nociceptin/orphanin FQ on the monosynaptic field potential may provide an in vitro model for the bidirectional actions of nociceptin/orphanin FQ in behavioural studies showing hyperalgesia at low doses of intrathecal nociceptin/orphanin FQ and analgesia at higher doses.