The present study describes the immunocytochemical distribution of peptides derived from the prodynorphin precursor in the brain of the rhesus monkey (Macaca mulatta). Animals were treated with colchicine (intracerebroventricularly) prior to perfusion to enhance the observation of perikaryal immunoreactivity. Using antisera generated against dynorphin A(1-17), dynorphin B(1-13), and prodynorphi...

Induction of prodynorphin gene expression by psychostimulant drugs may represent a compensatory adaptation to excessive dopamine stimulation and may contribute to the aversive aspects of withdrawal. We therefore investigated the molecular mechanisms by which dopamine psychostimulant drugs induce prodynorphin gene expression in vivo and in rat primary striatal cultures. We demonstrate that three...

We investigated the effect of long-term administration of opioid antagonists on the regulation of prodynorphin gene expression in rat brain. Intracerebroventricular (i.c.v.) injections for seven days of nor-binaltorphimine (nor-BNI), the highly selective kappa opioid antagonist, naloxone and its longer acting analog naltrexone, both relatively selective antagonists for the mu opioid receptor, m...

Orexins (also called hypocretins) are peptide neurotransmitters expressed in neurons of the lateral hypothalamic area (LHA). Mice lacking the orexin peptides develop narcolepsy-like symptoms, whereas mice with a selective loss of the orexin neurons develop hypophagia and severe obesity in addition to the narcolepsy phenotype. These different phenotypes suggest that orexin neurons may contain ne...

Zinc finger-containing transcription factor GATA-4 and homeodomain Nkx-2.5 govern crucial developmental fates and have been found to promote cardiogenesis in embryonic cells exposed to the differentiating agent DMSO. Nevertheless, intracellular activators of these transcription factors are largely unknown. In this study, pluripotent P19 cells expressed the prodynorphin gene, an opioid gene enco...

The distributions and extent of processing of four prodynorphin-derived peptides (dynorphin A (1-17), dynorphin A (1-8), dynorphin B, and alpha-neoendorphin) were determined in ten regions of the cortex as well as in the striatum of the guinea-pig. There were significant differences between concentrations of these peptides in most cortical regions, with alpha-neoendorphin being several times mo...

Neuropsychiatric disorders are one of the main challenges of human medicine with epilepsy being one of the most common serious disorders of the brain. Increasing evidence suggest neuropeptides, particularly the opioids, play an important role in epilepsy. However, little is known about the mechanisms of the endogenous opioid system in epileptogenesis and epilepsy. Therefore, we investigated the...

A vast body of evidence points to the role of the limbic system in the mechanism of drug dependence. Opioid peptides localized in the limbic system may play a role in central effects of substances of abuse. The goal of the present study was to investigate the influence of acutely and chronically administered drugs of abuse, cocaine and amphetamine on biosynthesis of prodynorphin and proenkephal...

We have previously demonstrated that [3H]dynorphin A selectively labels kappa opioid receptors in guinea-pig whole brain. In these current studies, using protection from inactivation by beta-chloronaltrexamine (beta-CNA), we are able to demonstrate that although dynorphin A prefers kappa receptors, it will label mu receptors when kappa receptors are not available, or present in only a small num...

Using radioactive in situ hybridisation, the distribution of prodynorphin mRNA in the brains of C57Bl/6 mice was systemically investigated, and double-labelling in situ hybridisation was used to determine the extent to which neuropeptide Y (NPY) and prodynorphin mRNAs were co-expressed. Our results demonstrate that prodynorphin mRNA expression in the mouse brain is localised at specific subregi...