Behavioral effects of endogenous or exogenous (mu, delta) opioid peptides: relation with DA mesolimbic pathways.
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Biomedical subjects
Publications and source records attributed to J Féger.
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The effects of CCK8 injected into the rat median nucleus accumbens on exploration and locomotion were measured in the four hole box and open-field tests. CCK8 (1 fmol to 100 pmol) induced hypoexploration in the four hole box (duration, frequency), with the pattern of the responses remaining unchanged compared to those of the control group. These effects were reversed by injection of the CCK antagonist proglumide (20 micrograms) into the nucleus accumbens. In the open-field test, CCK8 (100 pmol) only decreased locomotion and rearing when the rats were not habituated to the environment. These results show that the behavior of rats exposed to a novel external stimuli is highly sensitive to CCK8.
Administration of 3 fmol of cholecystokinin octapeptide (CCK8) into the postero-median nucleus accumbens (NAS) induced an hypoexploration measured using the four-hole box and an increase in the emotional states of rats observed in the elevated plus maze. These effects seem likely to involve CCKA receptors since they were reversed by the selective CCKA antagonist L364,718 (100 micrograms/kg, 200 micrograms/kg IP) and not observed after injection of 0.1 to 1000 fmol unsulfated cholecystokinin octapeptide (CCK8NS) in the same region. On the other hand, CCK8 or CCK8NS injected into the anterior NAS did not significantly modify these behaviors. These results support the neuroanatomical heterogeneity in the distribution of CCK and its binding sites in the NAS, but raise the question of the presence of CCKA receptors not detected in binding studies and of the behavioral effects mediated by CCKB receptor stimulation in this structure.
Hepatocytes were isolated from adult rats at various times after subcutaneous injection of turpentine (1 ml). The affinity to concanavalin A (Con A) of alpha 1-acid glycoprotein (AGP) and the intracellular content and rate of secretion of AGP and albumin were evaluated over a period of 19 days. Inflamed hepatocytes secreted mainly the Con A-reactive form of AGP whereas control hepatocytes secreted a higher amount of the Con A-non-reactive form. The intracellular content and rate of secretion of AGP by inflamed hepatocytes increased markedly whereas those of albumin decreased. However, when the residence time (ratio of intracellular content to rate of secretion) was evaluated, it appeared that the efficiency of secretion of both proteins was higher than in control hepatocytes. The changes in the affinity of AGP to Con A and in the secretion of AGP and albumin were reversible. These findings indicate that acute inflammation leads to posttranslational alterations during the intracellular transit of these secretory proteins.
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The concanavalin A-unreactive variants of alpha 1-acid glycoprotein introduced in culture medium of monocytes/macrophages induces the inhibition of thymocyte proliferative activity of interleukin 1. LPS or LPS receptors were not involved in the activity of alpha 1-acid glycoprotein on macrophages. alpha 1-acid glycoprotein did not show any direct effect on thymocytes whereas the monocyte/macrophage-supernatant inhibited the interleukin 1 proliferative effect. The activity of tumor necrosis factor and interleukin 2 was not altered by the alpha 1-acid glycoprotein-macrophage supernatant.
The carbohydrate analysis of alpha 1-AGPc purified from cirrhotic ascitic fluid was performed by immunoaffinity chromatography. It showed a large increase in the fucosyl molar ratio and sugar content (47%). The molar ratio of the oligosaccharides which were released by hydrazinolysis and fractionated by high-performance liquid chromatography confirms the marked increase in fucosyl residues in each fraction. A shift towards fractions with a high degree of branching was also observed. Moreover, the studies of sugar molar ratios and methylation of the tetrasialylated fraction indicated the simultaneous presence of sialyl and fucosyl residues on one of the outer branches.
The effects of iontophoretic applications of dopamine were studied on neurons of the subthalamic nucleus (STN) identified by their histological location, their response to contralateral vibrissae stimulation and, for 33% of them, by their antidromic activation from the globus pallidus. A potent and consistent excitatory effect of dopamine was found for all the STN neurons tested. Depression of spontaneous activity or mixed responses were never recorded in the STN. The excitatory response was antagonized by iontophoretic application of flupenthixol.
The effect of D-galactosamine on the structure of the glycan moiety of alpha 1-acid glycoprotein was studied throughout a nine days experiment. It was shown that: D-galactosamine led to an alteration of the Concanavalin A crossed immunoelectrophoresis pattern and to a decreased sialic acid content of alpha 1-acid glycoprotein. The undersialylation of alpha 1-acid glycoprotein was not linked to a change in the relative ratio of various Concanavalin A forms. At the end of the experiment (9 days after galactosamine injection), the Concanavalin A non-reactive forms of alpha 1-acid glycoprotein remained elevated whereas alanine transaminase activity, total protein and alpha-acid glycoprotein had returned to a control level. D-galactosamine-treated rats seem to be a suitable model for the study of the very fast cyclic modulations of the synthesis of the glycan moiety of glycoproteins.
Lipogenesis from U(14C) lactate was studied in hepatocytes isolated from obese Zucker rats (fa/fa) their lean littermates (Fa/?) and Sprague Dawley rats. The distribution of radioactive carbon between the glycerol and the fatty acid moieties of the acylglycerols were studied. Radioactive lactate was better utilized for glycerol formation than it was for fatty acid formation in the obese rats. However, when oleate was added to the hepatocytic incubation medium, radioactive lactate was preferentially incorporated into the fatty acid moiety of the acylglycerols. Zucker obesity classified as a "metabolic obesity" by Meyer (1) depends upon abnormalities in carbohydrate metabolism associated with increased lipogenesis. This might be explained by biochemical shifts in the utilization of nutrients (2). Among the nutrients, lactate seems to be a better source of carbon than glucose for lipid synthesis (3). It has been shown that there is an increased hepatic portal blood concentration of lactate several hours after eating: about 4 mM in Wistar rats (4) and 10-15 mM in obese Zucker rats (3). We are interested in determinating the incorporation of carbon from lactate either into glycerol or into fatty acyl moieties of hepatic acylglycerols, and in determining the influence of exogenous fatty acids on acylglycerol synthesis, since a high level of circulating fatty acids in Zucker obese rats has been reported (5). Our purpose was to determine the incorporation of lactate into glycerol and fatty acyl moieties of acylglycerols, under the influence of oleate. Hepatocytes were isolated from ad libitum fed obese Zucker rats (fa/fa), their lean littermates (Fa/?) and Sprague-Dawley rats (SD). Incorporation of lactate was studied for three hours, in order to exclude short-term regulation effects and to allow oleate to be distributed into all cellular compartments.
Fluorescent tracers (Nuclear Yellow, True Blue, Fast Blue) were injected, in various combinations, into the globus pallidus and substantia nigra in three marmosets. Examination of perikarya in the ipsilateral neostriatum, well removed from pallidal injection sites, revealed that the predominant pattern was of single-labelled cells, retrogradely labelled from either the globus pallidus or substantia nigra. It is suggested, on the basis of this evidence and data previously available, that the striatum contains at least three types of efferent neurones, one projecting exclusively to the globus pallidus, one projecting exclusively to the substantia nigra, and another projecting to both structures.
Reciprocal projections between the subthalamic nucleus of the diencephalon and the brain stem nucleus tegmenti pedunculopontinus have been demonstrated and studied anatomically and electrophysiologically in the rat. Injections of the fluorescent compound Fast Blue into pedunculopontinus and the surrounding peribrachial region of the mesencephalon gave rise to retrogradely-labelled neurone cell bodies in the ipsilateral subthalamic nucleus. A minimum of 1% of subthalamic nucleus neurones appeared to contribute to this projection. Electrical stimulation of the subthalamic nucleus in chronically decorticated rats resulted in inhibition of extracellularly recorded ipsilateral pedunculopontine cells which had themselves been identified (by antidromic activation) as projecting rostrally as far as the subthalamic nucleus or entopeduncular nucleus. Injection of the enzyme horseradish peroxidase into the subthalamic nucleus resulted in retrograde labelling of neurones in the ipsilateral nucleus tegmenti pedunculopontinus with additional contralateral labelling in some animals. Similar pedunculopontine labelling was not seen after injection of horseradish peroxidase into either the zona incerta or lateral hypothalamus. Stimulation of the subthalamic nucleus gave rise to antidromic activation of some neurones in nucleus tegmenti pedunculopontinus. The rate of conduction of the pedunculopontine-subthalamic projection was estimated to be approximately 1.7 m/s. Electrical stimulation of pedunculopontinus gave rise to orthodromic activation of some subthalamic nucleus neurones which had themselves been identified (by antidromic activation) as projecting to the globus pallidus or substantia nigra. The nucleus tegmenti pedunculopontinus is in a position to fulfill two roles--to control the activity of rostrally-located motor centres such as the globus pallidus, entopeduncular nucleus, subthalamic nucleus and substantia nigra and, by reciprocal connections, to mediate in part the effects of these structures on the lower motor system. The observations presently described are a first step in the analysis of the potential role of the pedunculopontine nucleus in the modulation of activity in, and the mediation of activity from, the basal ganglia and related motor structures of the diencephalon and mesencephalon.
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The aim of the present study was to test the GABAergic nature of the inhibitory projection from substantia nigra, pars reticulata (SNr) to superior colliculus (SC) in the rat, through the use of extracellular recordings and microiontophoresis. The effect of SN stimulation on the spontaneous or glutamate-evoked firing of SC units was analyzed. Among 28 SC cells inhibited by SNr stimulation, 27 decreased their firing rate following iontophoretic application of either GABA or glycine. The effect of the iontophoretic administration of bicuculline on SN4-evoked inhibition was studied on 14 of these GABA- and glycine-sensitive neurons. Bicuculline reversibly blocked nigral inhibition on 12 neurons, with iontophoretic current which did not affect glycine depression. These results are consistent with the hypothesis that GABA is the inhibitory transmitter of the nigrotectal projection.
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The possible correlation between sialic acid content of hepatocyte plasma membranes, and their binding capacity was investigated. For that purpose, [3H] asialotransferrin binding was tested with hepatocytes from both normal and streptozotocin treated rats. The observed decrease in binding capacity was parallel to a decrease in the sialic acid content Insulin therapy restored simultaneously normal blood glucose level, hepatic membrane sialic acid content and binding capacity.
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