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L Terenius

Publications and source records attributed to L Terenius.

At least 109 records · Page 6Linked to original sources
PubMed1994

The striatonigral dynorphin pathway of the rat studied with in vivo microdialysis--II. Effects of dopamine D1 and D2 receptor agonists.

In vivo microdialysis was used to study the effect of intracerebral administration of dopamine agonists on dynorphin B release in the striatum and substantia nigra of rats. The release of dopamine and GABA was also investigated. Administration of the dopamine D1 agonist SKF 38393 (10-100 microM) into the striatum increased extracellular dynorphin B and GABA levels in the ipsilateral substantia nigra, in a concentration-dependent manner. After a short-lasting increase, nigral dopamine levels were significantly decreased after the highest concentration of striatal SKF 38393. An increase in striatal dynorphin B, GABA and dopamine levels was also observed. When SKF 38393 (10 microM) was administered into the substantia nigra, nigral dynorphin B and GABA, but not dopamine levels increased. No significant effects were observed on striatal levels. Administration of the dopamine D2 agonist, quinpirole (100 microM), into the striatum decreased dopamine levels in both striatum and substantia nigra, while no effect was observed on striatal or nigral dynorphin B and GABA levels. Quinpirole (10-100 microM) given into the substantia nigra, decreased striatal dopamine levels in a concentration manner. In the nigra, a short-lasting increase in dopamine levels was observed following the highest concentration of nigral quinpirole (100 microM). The effect was followed by a decrease in dopamine levels. No significant effects were observed on striatal or nigral dynorphin B and GABA levels. The results show that stimulation of D1 receptors in striatum and substantia nigra leads to activation of the striatonigral dynorphin pathway. A parallel effect could also be seen on nigral GABA release.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1994

Differences between alcohol-preferring (AA) and alcohol-avoiding (ANA) rats in the prodynorphin and proenkephalin systems.

The motivation to drink alcohol and the eventual risk of becoming addicted are in part genetically determined. Because opioid peptides are considered central to motivated behaviors, we have analyzed opioid peptides in relevant areas of the brain of two outbred lines of rats: the alcohol-preferring [Alko Alcohol (AA)] line who voluntarily drink alcohol and the alcohol-avoiding [Alko Non-Alcohol (ANA)] line with negligible intake. (Met)enkephalinArg6Phe7 (MEAP) was measured as a marker of proenkephalin, and dynorphin A, dynorphin B, and (Leu)enkephalinArg6 as markers of the prodynorphin system. The major line differences and effects of alcohol intake were observed in mesolimbic brain areas. The mesolimbic dopamine pathway, which projects from the ventral tegmental area (VTA) to the nucleus accumbens, is central in the reward system. Basal levels of MEAP and dynorphin peptides were low in the nucleus accumbens of AA rats, whereas (Leu)enkephalinArg6 levels were lower in the VTA of these rats. Alcohol drinking caused MEAP levels in the accumbens to rise, but had no effect on prodynorphin peptides. Opioids also influence the nigrostriatal dopamine pathway. However, this study showed no significant differences for any peptide between rat lines, or effect of alcohol intake, in either substantia nigra or striatum, except for a decrease of nigral and striatal (Leu)enkephalinArg6 levels in alcohol-drinking AA rats. Large line differences were observed in the pituitary gland. AA rats had high basal levels of MEAP, which became even higher after voluntary alcohol consumption for 4 weeks, and low levels of dynorphin peptides, not affected by alcohol drinking.(ABSTRACT TRUNCATED AT 250 WORDS)

Alcohol Drinking↗
PubMed1993

GAP-43, aFGF, CCK and alpha- and beta-CGRP in rat spinal motoneurons subjected to axotomy and/or dorsal root severance.

The mRNA levels for growth-associated protein 43 (GAP-43), acidic fibroblast growth factor (aFGF), alpha- and beta-calcitonin gene-related peptide (CGRP), cholecystokinin (CCK) and choline acetyltransferase (ChAT) in rat lumbar spinal motoneurons were studied by in situ hybridization 1, 5 and 21 days and 20 weeks following unilateral peripheral nerve sectioning, ventral rhizotomy or dorsal rhizotomy. Furthermore, CGRP- and aFGF-like immunoreactivities in the ventral horn were studied using immunohistochemistry. One to 21 days after axotomy, GAP-43 and alpha-CGRP mRNAs increased in lesioned motoneurons, while the aFGF mRNA levels were marginally higher in motoneurons on the lesion side as compared to the control side. beta-CGRP, CCK and ChAT mRNA levels, on the other hand, decreased during the short-term response (1-21 days) to axotomy. After ventral rhizotomy, but not peripheral axotomy, there was complete disappearance of aFGF-like immunoreactivity in the ventral root proximal to the lesion. In animals subjected to long-term survival (20 weeks) after peripheral axotomy, the expression of all studied substances had returned to normal levels. Unilateral dorsal rhizotomy did not induce any substantial short- or long-term shifts in the cellular expression of the GAP-43, aFGF, CGRP and CCK peptides or their mRNAs in motoneurons of lesioned segments. These results indicate that peptides/proteins in motoneurons are expressed differentially after axotomy. Whereas alpha-CGRP and GAP-43 are up-regulated, CCK and beta-CGRP become down-regulated and aFGF is largely unaffected.

Animals↗
PubMed1993

CGRP-like immunoreactivity in A11 dopamine neurons projecting to the spinal cord and a note on CGRP-CCK cross-reactivity.

Using the indirect immunofluorescence technique and double labelling procedures combined with retrograde tracing it could be demonstrated that the A11 dopamine cell group, located at the border between the diencephalon and mesencephalon of the rat brain and some of which project to the spinal cord, contains calcitonin gene-related peptide (CGRP)-like immunoreactivity. Thus, another catecholamine group in the rat brain has been shown to have a coexisting peptide. One of the CGRP antisera used in the present study also stained cholecystokinin (CCK) containing neurons in various brain areas. Absorption and displacement experiments using immunohistochemistry and radioimmunoassay showed that this cross-reactivity was confined to the C-terminal portion of the peptide molecule. Therefore, the present results suggest that CGRP antisera used for immunohistochemistry and radioimmunoassay should be tested for possible cross-reactivity with CCK.

Animals↗
PubMed1993

NF-kappa B-like factors in the murine brain. Developmentally-regulated and tissue-specific expression.

NF-kappa B and related factors are important transducers of external signals to the cell nucleus. They are abundant in the brain, where they may be significant for the regulation of gene transcription in plasticity-related processes for instance, via activation of protein kinase C. The subunit composition and levels of these factors in the mouse and rat brain and other tissues, using an assay based on gel retardation of the oligonucleotides corresponding to the kappa B DNA-element, are reported here. Three major kappa B-binding factors were observed. Factors I and II were activated by the dissociating agent deoxycholate. DNA protein cross-linking and antibody neutralization experiments suggest that factor I is a heterodimer of c-Rel and p65; factor II is a heterodimer of p50 and p65 (authentic NF-kappa B), and of p50 and c-Rel; factor III is the p50 homodimer (KBF1). All three factors were generally expressed in the 17-day-old rat embryo and 5-day-old pup, whereas in the adult rat, expression was more limited and showed certain tissue specificity. Factor II was the most generally expressed and the only factor observed in adult brain. Factor I was only detected in the adult testis whereas factor III was observed in the adult spleen and, in small amounts, in the liver and lung. Two minor kappa B-specific factors (A and B), distinctive to the brain and spleen, respectively, showed very slow gel mobility. Their estimated molecular weights were about 125 kDa and 95 kDa, respectively. Expression of factor A was stable in the rat brain during development. Factor A may be identical to a previously described brain-specific factor, BETA (Korner et al., Neuron, 3 (1989) 563-572). Thus, the expression pattern of kappa B-binding activities is apparently developmentally regulated and tissue-specific particularly in the adult. In the adult mouse and rat brain, only factors II (probably NF-kappa B and p50/c-Rel heterodimer) and A (probably BETA) could be observed.

Animals↗
PubMed1993

Immunohistochemical evidence for a neurotensin striatonigral pathway in the rat brain.

The distribution and origin of neurotensin-like immunoreactivity in the substantia nigra pars reticulata of the rat have been analysed using immunohistochemistry combined with different drug treatments and lesioning techniques. In normal rats, a distinct but weakly fluorescent network of neurotensin-immunoreactive fibers was found in the central part of the substantia nigra pars reticulata. When the animals were treated with reserpine, which suppresses dopamine transmission, a similar pattern of immunoreactivity was found, though the intensity of staining was slightly enhanced. However, when rats were treated with methamphetamine, a potent dopamine releaser, the intensity of immunoreactivity was dramatically increased. In particular, densely packed neurotensin-immunoreactive fibers were found at the dorsal border and at the ventral periphery of the substantia nigra pars reticulata. This pattern of immunoreactivity was found to be similar to that displayed by dynorphin. In the nucleus caudatus, several neurotensin-immunoreactive cell bodies were seen after reserpine treatment. Morphologically similar perikarya were observed in methamphetamine-treated rats, but they were less numerous, whereas no cell bodies were detectable in untreated animals. When a unilateral mechanical transection or an ibotenic acid injection was performed in the striatum, the patterns of neurotensin as well as dynorphin and substance P immunoreactivities in the substantia nigra pars reticulata were strongly affected. Both types of lesion caused a marked, parallel depletion of all three immunoreactive substances on the side ipsilateral to the lesion, where a restricted area was virtually devoid of immunoreactive elements. Thus the present study provides evidence for the existence of a unilateral neurotensin striatonigral pathway, terminating in the pars reticulata. The origin of the neurotensin fibers in the pars compacta has not been established but does not appear to be the caudate nucleus. These results together with evidence from the literature suggest that methamphetamine induced a massive release of dopamine from nigral dendrites acting on presynaptic D1 dopamine receptors located on neurotensinergic terminals leading to a marked increase in neurotensin-like immunoreactivity in the pars reticulata.

Animals↗
PubMed1993

Peptide-immunoreactive neurons and nerve fibres in lumbosacral sympathetic ganglia: selective elimination of a pathway-specific expression of immunoreactivities following sciatic nerve resection in kittens.

The distributions of peptide-immunoreactive nerve fibres and cell bodies in lumbosacral paravertebral sympathetic ganglia of young cats were analysed with antibodies to calcitonin gene-related peptide, enkephalin, neurotensin, somatostatin, substance P, galanin, neuropeptide Y and vasoactive intestinal polypeptide. Fairly dense networks of nerve fibres showing enkephalin-, neurotensin-, somatostatin- or substance P-like immunoreactivity were observed in the ganglia. Double-staining experiments revealed that enkephalin- and somatostatin-immunoreactive nerve fibres preferentially surrounded calcitonin gene-related peptide- and/or vasoactive intestinal polypeptide-immunoreactive cell bodies. Neurotensin- and substance P-immunoreactive nerve fibres were mainly associated with neurons showing neuropeptide Y and/or galanin-like immunoreactivity. Occasional nerves containing calcitonin gene-related peptide-, galanin-, neuropeptide Y- or vasoactive intestinal polypeptide-like immunoreactivity were observed. These fibres did not seem to have any direct regional distribution within the ganglia. In kittens surviving for three months after early postnatal sciatic nerve resection, no calcitonin gene-related peptide-immunoreactive cell bodies could be detected in ganglia ipsilateral to the operation. In contrast, vasoactive intestinal polypeptide-like immunoreactivity, which partly co-exists with calcitonin gene-related peptide, was observed to the same extent as in control ganglia. Furthermore, almost all of the somatostatin-immunoreactive varicose nerve fibres had disappeared, whereas a fairly dense network of calcitonin gene-related peptide-immunoreactive nerve fibres could be observed. This change was paralleled by an increased content of nerve fibres that were immunoreactive to antibodies against the growth-associated protein GAP-43 (also known as B-50). The present findings suggest that experimental perturbations where postganglionic neurons are separated from their target areas by axotomy, not only induce differential changes in neurotransmitter expression in the principal ganglion cells, but also in preganglionic sympathetic neurons projecting to the ganglia. One possible explanation for the occurrence of an axotomy-induced network of calcitonin gene-related peptide-immunoreactive nerve fibres, is that extrinsic sensory nerve fibres grow into the ganglia after the sciatic nerve lesion. Thus, these findings seem to suggest one additional possibility with regard to the question of a possible interaction between sympathetic and sensory neurons after peripheral nerve injury.

Animals↗
PubMed1993

Opiate receptors--the historical breakthrough in drug research.

Morphine (Fig. 1) remains the most powerful analgesic but its therapeutic value is compromised by its strong reinforcing properties, making it highly addictive. This has stimulated the quest to find an analgesic lacking dependence-producing properties. So far no such drug has been discovered. However, this search has helped to disclose the large range of endogenous opioid peptides and the various receptors on which they act. This diversity and opportunity for interaction between exogenous drug and endogenous peptide, makes opiate dependence, tolerance and withdrawal complicated phenomena that are not fully understood at the molecular and cellular levels. The occurrence of opiate receptors in 'reward' pathways also makes them possible targets for the treatment of other addictions, adding a further dimension to the picture.

Animals↗
PubMed1992

A selective and extremely potent antagonist of the neurokinin-1 receptor.

Sendide [Tyr6,D-Phe7,D-His9]-substance P(6-11) has been examined by measurements of ligand binding to crude membrane fractions and by functional tests on the spinally mediated behavioral response. Sendide potently displaced [3H]-labeled substance P (SP) binding to mouse spinal cord membranes in a competitive manner. In vivo, sendide, intrathecally co-injected with SP, competitively antagonized SP-induced scratching, biting and licking. The behaviors elicited by physalaemin, septide and [Sar9, Met(O2)11]-SP were also reduced by co-administration of sendide. Large doses of sendide were needed to reduce the action of neurokinin A, D-septide, neurokinin B and eledoisin. The in vitro and in vivo pharmacological profile of sendide demonstrated that it is a selective and extremely potent antagonist of the neurokinin-1 receptor.

Amino Acid Sequence↗
PubMed1992

Presence of a dynorphin-like peptide in a restricted subpopulation of catecholaminergic neurons in rat nucleus tractus solitarii.

Immunofluorescence colocalization techniques were used to examine the extent of coexistence of the endogenous opioid peptide dynorphin with catecholamines and the related opioid peptide enkephalin within neurons of the rat medulla oblongata. Immunoreactivities for dynorphin and the catecholamine-synthesizing enzyme tyrosine hydroxylase were found to coexist within a limited subpopulation of A2 catecholamine cells, localized to the medial nucleus of the nucleus tractus solitarii. Colocalization of the two opioid peptides was found mainly within perikarya situated in the medial and ventrolateral nuclei of the nucleus tractus solitarii. Triple-labeling studies revealed only rare cases of catecholamine/dynorphin/enkephalin coexistence. These data demonstrate that dynorphin is present within a restricted subpopulation of catecholamine neurons in the dorsal medulla oblongata. In addition, the content of either of the opioids enkephalin or dynorphin appears to distinguish subsets of medullary catecholamine neurons.

Animals↗
PubMed1992

Reappearance of calcitonin gene-related peptide-like immunoreactivity in the dorsal horn in the long-term dorsal root transected rat.

Calcitonin gene-related peptide (CGRP)-immunoreactive (IR) fibers in the rat dorsal horn superficial laminae vanish almost completely 3 weeks following unilateral dorsal rhizotomy. After a prolonged survival (20 weeks) of dorsal rhizotomy there is, however, a reappearance of CGRP-IR fibers in the corresponding laminae of the dorsal horn. The density of such IR fibres showed a clear gradient with the lowest number found in the midlesion region and an increase in density towards the neighboring, intact segments. In normal as well as lesioned rats, no neurons intrinsic to the dorsal horn contained detectable levels of CGRP-like immunoreactivity (LI). Furthermore, no cells could, by use of in situ hybridization, be demonstrated to contain detectable levels of mRNA encoding for CGRP in the dorsal horn. Based on these findings, we suggest that the CGRP-IR fibers observed following long-term survival of dorsal rhizotomy derive from proliferating collateral branches of primary afferents of neighboring intact segments.

Animals↗
PubMed1992

Isolation of a hemoglobin-derived opioid peptide from cerebrospinal fluid of patients with cerebrovascular bleedings.

The hemorphins are peptides with opioid activity, which are enzymatically released from hemoglobin. A decapeptide identical to the sequence 32-41 of the beta-, delta-, gamma- or epsilon-chains of hemoglobin has been isolated from human ventricular cerebrospinal fluid (CSF). The peptide, designated LVV-hemorphin-7, was recovered in relatively high amounts (115-300 pmol per ml) from samples of patients with cerebrovascular bleedings, but was not detectable in control CSF. Its identity with the hemoglobin fragment was confirmed by mass spectrometry and gas-phase sequencing.

Amino Acid Sequence↗
PubMed1992

Distribution of enkephalin and its relation to serotonin in cat and monkey spinal cord and brain stem.

The distribution of enkephalin (ENK)-like immunoreactivity (LI) in spinal cord and medulla oblongata of cat and gray monkey (Macaca fascicularis) was studied by use of immunofluorescence and peroxidase antiperoxidase (PAP) techniques. Possible coexistence between ENK- and 5-hydroxytryptamine (5-HT)-LI was also analyzed with double labeling immunofluorescence. Furthermore, in situ hybridization was used to demonstrate cell bodies in the brain stem expressing mRNA encoding for ENK. ENK-immunoreactive (IR) axonal varicosities and fibers were demonstrated throughout the spinal cord gray matter, with the highest density in the superficial dorsal horn, the area around the central canal, the intermediolateral cell column, the sacral parasympathetic nucleus, and in Onuf's nucleus. In the monkey ventral horn, ENK-IR varicose fibers could in some cases be demonstrated in very close apposition to cell bodies. A low degree of co-localization between ENK- and 5-HT-LI was seen in the spinal cord of both species. Still, fibers containing both compounds could as a rule be demonstrated in every section studied. The highest degree of coexistence was encountered in the motor nucleus of the ventral horn. Six weeks after a low thoracic spinal cord transection a decreased staining for ENK-LI was demonstrated in the ventral horn motor nucleus, whereas other parts of the spinal cord appeared unaffected. In the brain stem of cats after colchicine treatment, ENK-LI was found in a majority of the 5-HT-IR cell bodies in the raphe nuclei (nucleus raphe magnus, pallidus and obscurus) and in the lateral reticular nucleus (rostroventrolateral reticular nucleus). In cat not pretreated with colchicine, a few weakly stained ENK-IR cell bodies could be found in the midline raphe nuclei and in the lateral reticular nucleus with the PAP technique. In the monkey brain stem without colchicine treatment, using the PAP technique, heavily stained ENK-IR cell bodies could be seen in the lateral reticular nucleus whereas, as in the cat, only a few, weakly stained ENK-IR cell bodies could be seen in the midline raphe nuclei. Using in situ hybridization technique, ENK mRNA expressing cells were demonstrated in the lateral reticular nucleus while no convincing mRNA signal could be found over cell bodies in the raphe nuclei. It is concluded that part of the ENKergic innervation of the cord in both species derives from supraspinal or suprasegmental levels.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗