1,721,143 research outputs found
Chronic GBR 12909 administration differentially alters prodynorphin gene expression compared to cocaine
No full textThe effect of the selective dopamine uptake inhibitor 1-[2-[bis(4-flourophenyl)methoxy]ethyl]-4-[3-phenylpropyl]piperazine dihydrochloride (GBR 12909) was examined on prodynorphin gene expression. GBR 12909 or vehicle was continuously infused for 7 days via osmotic minipump, or injected daily into male rats. Both continuous infusions and daily injections of GBR 12909 produced significant decreases in prodynorphin expression in the hypothalamus (37% and 31% decreases, respectively). There were no significant changes in the caudate putamen, hippocampus or nucleus accumbens. One injection of GBR 12909 had no effects on prodynorphin expression in any of the brain regions studied, suggesting that the effect in the hypothalamus is not an acute effect. As previously reported for other treatment regimens, continuous infusion of cocaine produced a 35% significant decrease in the hypothalamus, consistent with the effects of GBR 12909. In contrast to GBR 12909, however, cocaine also produced a significant increase in prodynorphin expression in the caudate putamen. Thus, chronic inhibition of dopamine uptake can regulate prodynorphin expression in the hypothalamus. In contrast, the increase in the caudate putamen following cocaine administration may not be related to the inhibition of dopamine uptake, since it was not produced by a selective dopamine uptake inhibitor. These findings suggest that regulation of prodynorphin gene expression by cocaine in the caudate putamen may be mediated by the inhibition of norepinephrine or serotonin uptake, by a combination of effects on two or three monoamine transporters, or by a mechanism unrelated to transporter inhibition. © 2001 Published by Elsevier Science B.V
Dynorphin and epilepsy
No full textStudies on dynorphin involvement in epilepsy are summarised in this review. Electrophysiological, biochemical and pharmacological data support the hypothesis that dynorphin is implicated in specific types of seizures. There is clear evidence that this is true for complex partial (limbic) seizures, i.e. those characteristic of temporal lobe epilepsy, because: (1) dynorphin is highly expressed in various parts of the limbic system, and particularly in the granule cells of the hippocampus; (2) dynorphin appears to be released in the hippocampus (and in other brain areas) during complex partial seizures; (3) released dynorphin inhibits excitatory neurotransmission at multiple synapses in the hippocampus via activation of κ opioid receptors; (4) κ opioid receptor agonists are highly effective against limbic seizures. Data on generalised tonic-clonic seizures are less straight forward. Dynorphin release appears to occur after ECS seizures and κ agonists exert a clear anticonvulsant effect in this model. However, more uncertain biochemical data and lack of efficacy of κ agonists in other generalised tonic-clonic seizure models argue that the involvement of dynorphin in this seizure type may not be paramount. Finally, an involvement of dynorphin in generalised absence seizures appears unlikely on the basis of available data. This may not be surprising, given the presumed origin of absence seizures in alterations of the thalamo-cortical circuit and the low representation of dynorphin in the thalamus. In conclusion, it may be suggested that dynorphin plays a role as an endogenous anticonvulsant in complex partial seizures and in some cases of tonic-clonic seizures, but most likely not in generalised absence. This pattern of effects may coincide with the antiseizure spectrum of selective κ agonists
Kindled seizure-induced c-fos and prodynorphin mRNA expressions are unrelated in the rat brain
No full textLevels of mRNA for c-fos and prodynorphin were studied by in situ hybridization in adjacent coronal sections taken from kindled rats 30-60 min after the last seizure. Within this time frame, expression of both genes was induced in multiple brain areas. Anatomical colocalization of the induced gene expressions was found in the hippocampus. Induction of c-fos in the dentate gyrus was bilateral and symmetrical in a subgroup of rats, ipsilateral in another subgroup and absent in a third subgroup. However, no relative increase was observed in the ipsilateral compared with the contralateral prodynorphin expression in the dentate gyrus when c-fos expression was induced ipsilaterally only. These observations suggest that, at variance with other experimental situations, Fos is not involved in the mechanisms of kindled seizure-induced activation of prodynorphin transcription in the rat forebrain
Chronic intracerebroventricular cocaine differentially affects prodynorphin gene expression in rat hypothalamus and caudate-putamen
No full textWe investigated the effects of sustained administration of cocaine on the regulation of prodynorphin gene expression in rat brain. Intracerebroventricular (i.c.v.) infusion of cocaine hydrochloride (30 μg/day) for 7 days, by means of osmotic minipumps, elicited a significant 35% decrease of prodynorphin mRNA levels in rat hypothalamus and increase (22%) in caudate-putamen. At the same time and in the same animals, no significant changes were detected in the hippocampus or in the nucleus accumbens. These results indicate that continuously infused cocaine is able to modulate expression of the prodynorphin gene in opposite directions or has no effect on prodynorphin expression, depending on the brain region analysed. Cocaine, as well as opiates, might activate specific neuronal pathways, shared by different classes of drugs of abuse, involving, at least in part, the endogenous opioid system
The effect of paracetamol on nociception and dynorphin A levels in the rat brain
No full textMale Wistar rats were administered with naloxone (1 mg/kg i.p.) or MR 2266 (5 mg/kg i.p) 15 min before paracetamol (400 mg/kg i.p.) treatment and the pain threshold was evaluated. Rats were subjected to the hot-plate and formalin tests and immunoreactive dynorphin A (ir-dynorphin A) levels were measured in the hypothalamus, hippocampus, striatum, brainstem, frontal and parietal-temporal cortex by radioimmunoassay. Pretreatment with naloxone abolished paracetamol antinociceptive activity both in hot-plate and in the first phase, but not in the second phase of the formalin test, while MR 2266 pretreatment was able to antagonise paracetamol effect either in the hot-plate test or in both phases of the formalin test. Among different brain areas investigated paracetamol significantly decreased ir-dynorphin A levels only in the frontal cortex. MR 2266 but not naloxone reversed the decrease in ir-dynorphin A levels elicited by paracetamol. Paracetamol seems to exert its antinociceptive effect also through the opioidergic sistem modulating dynorphin release in the central nervous system (CNS) of the rat, as suggested by the decrease in the peptide levels. © 2001 Harcourt Publishers Ltd
Vasoactive intestinal polypeptide carboxy-terminal fragment, VIP(22-28), and other fragments of VIP, in the central nervous system of the rat
No full textThe possible existence in rat brain tissues of shorter peptides related to VIP has been examined. VIP and PHI both contain paired basic amino acid residues at which posttranslational cleavage of these peptides might occur. Antiserum to VIP(22-28) was raised in rabbits. The antiserum was carboxy-terminus directed, showing cross-reactivity with all tested peptides containing the VIP carboxy-terminus sequences. Chromatographic analysis of rat brain extracts demonstrated that recovered VIP(22-28) immunoreactivity [VIP(22-28)-ir] was heterogeneous, consisting of a major fraction [60-70% of total VIP(22-28)-ir] which eluted as authentic VIP(1-28) on gel filtration and on reversed phase high performance liquid chromatography (HPLC) columns. A second fraction (30-35% of total VIP(22-28)-ir] eluted from gel filtration columns in the position of VIP(22-28). HPLC analysis of this fraction from extracts of rat cortex, hippocampus, and midbrain indicated that it was heterogeneous. One component corresponded to authentic VIP(22-28). The other two components have not been identified; one appears to be a VIP fragment intermediate in size between VIP(1-28) and VIP(22-28). © 1989
The effect of a paracetamol and morphine combination on dynorphin A levels in the rat brain
No full textThe purpose of this study was to find out whether the combination of inactive doses of paracetamol (PARA) and morphine was able to change dynorphin (DYN) A levels, evaluated by radioimmunoassay, and whether naloxone or [(-)-2-(3 furylmethyl)-normetazocine] (MR 2266), a κ-opioid antagonist, modifies or prevents the activity of this combination on nociception and on DYN levels. The work was suggested by our previous findings which demonstrated that inactive doses of PARA and morphine, when given in combination, share an antinociceptive effect, and that PARA, at antinociceptive doses, decreases DYN levels in the frontal cortex, thus indicating a selective action within the CNS. Our present results demonstrate that the combination of inactive doses of PARA (100 mg/kg) and morphine (3 mg/kg) is just as effective in decreasing the levels of DYN A as full antinociceptive doses of PARA or morphine alone in the frontal cortex of the rat. The values, expressed in pmol/g tissue, were: control = 2.83 ± 0.20; paracetamol (100) = 2.60 ± 0.23; morphine (3) = 2.73 ± 0.24; paracetamol + morphine = 1.34 + 0.16 (P < 0.05). The decrease was partially antagonised by MR 2266, but not by naloxone, suggesting that the activity of PARA and morphine in combination on DYN A levels could be mediated, at least in part, through κ-receptors, although other systems may be involved. On the other hand, both naloxone and MR 2266 prevented the antinociceptive effect of the combination in the hot plate test. All our experimental data suggest that PARA and morphine in combination exert their antinociceptive effect through the opioidergic system, which in turn may cause a decrease in DYN levels in the CNS of the rat. © 2001 Elsevier Science Inc
Studies of anti-phospholipase A2 and anti-inflammatory activites of a synthetic nonapeptide from uteroglobin
No full textThe nonapeptide H-Met-Gln-Met-Lys-Lys-Val-Leu-Asp-Ser-OH (antiflammin), corresponding to a high amino acid similarity region of uteroglobin was prepared by solution and solid phase synthesis. The peptide do not inhibit pancreatic phospolipase A2 in vitro and the carrageenin-induced oedema in vivo
Modulation of proorphaninFQ/N gene expression by morphine in the rat mesocorticolimbic system
No full textWe studied the effects of acute and chronic morphine treatment on proorphaninFQ/N (proOFQ/N) gene expression in the mesocorticolimbic system, known to be a reward-relevant area, of the rat CNS. Northern blot analysis revealed that a single injection of morphine 10 mg/kg i.p. increased proOFQ/N mRNA levels in nucleus accumbens, temporo-parietal cortex and in striatum. The chronic administration of the opiate caused a significant increase of proOFQ/N mRNA levels in the ventral tegmental area and a decrease in the striatum and in the nucleus accumbens. No changes were observed in the prefrontal cortex. These data indicate for the first time that morphine alters proOFQ/N gene expression in mesocorticolimbic areas, supporting the direct interaction between the opioid and OFQ/N systems and the OFQ/N involvement in morphine-rewarding mechanisms. © 2002 Lippincott Williams & Wilkins
Binding profile of benextramine at neuropeptide Y receptor subtypes in rat brain areas
No full textBinding studies in rat whole brain, frontoparietal cortex and brainstem membrane preparations revealed that benextramine displayed [3H]neuropeptide Y specific binding from a low and a high affinity site with IC50 values in the μM (36 ± 2, 4.4 ± 1.4 and 300 ± 120 μM, respectively) and the pM (29.3 ± 12.1, 0.35 ± 0.11 and 0.42 ± 0.03 pM, respectively) range, whereas in rat hippocampus benextramine displaced [3H]neuropeptide Y specific binding from one site only with an IC50 value of 22.8 ± 5.7 μM. With the exception of frontoparietal cortex binding assay, benextramine was not able to completely inhibit [3H]neuropeptide Y specific binding revealing the presence of a benextramine nonsensitive third binding site. Benextramine pretreatment followed by membrane washing demonstrated that benextramine inhibited irreversibly both high and low affinity sites. © 1994
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