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J Glowinski

Publications and source records attributed to J Glowinski.

584 records · Page 33Linked to original sources
PubMedDate not supplied

Identification of presynaptic serotonin autoreceptors using a new ligand: 3H-PAT.

Binding studies with appropriate labelled ligands have revealed the existence of two types of serotonin (5-HT) receptor, 5-HT1 and 5-HT2, in the central nervous system of mammals. The 5-HT1 type is characterized by a higher affinity for agonists than for antagonists, whereas the 5-HT2 type binds preferentially to antagonists. However, neither of these receptor types apparently corresponds to the presynaptic autoreceptor controlling 5-HT release. In an attempt to identify the presynaptic autoreceptor directly, we synthesized the tritiated derivative of 8-hydroxy-2-(di-n-propylamino) tetralin (PAT), a new tetralin derivative with potent 5-HT agonist properties and carried out binding studies with rat brain membranes. As we report here, in the hippocampus, the properties of 3H-PAT binding sites correspond closely to those of 5-HT1 sites. In contrast, in the striatum, 3H-PAT binding sites exhibit a subcellular distribution and pharmacological characteristics usually associated with presynaptic autoreceptors. Furthermore, a marked loss of 3H-PAT binding sites occurs in the striatum (but not in the hippocampus) after the selective degeneration of serotoninergic fibres in 5,7-hydroxytryptamine (5,7-HT)-treated rats. Conversely, the sprouting of additional 5-HT terminals in the brain stem of adult rats treated at birth with 5,7-HT is associated with an increased density of 3H-PAT binding sites in this region. 3H-PAT thus seems to be a useful ligand for studying the biochemical and pharmacological characteristics of presynaptic autoreceptors in selected regions of rat brain.

8-Hydroxy-2-(di-n-propylamino)tetralin↗
PubMedDate not supplied

Glial heterogeneity may define the three-dimensional shape of mouse mesencephalic dopaminergic neurones.

The shape of a neurone--the projection and branching pattern of axons and dendrites--appears to be determined by a combination of intrinisic and environmental influences. We have previously shown that striatal target neurones influence the biochemical maturation of ascending mesencephalic dopamine (DA) cells in culture, as well as the elongation rate of DA neurites. Using a similar approach in which the morphology of individual DA cells can be studied after 3H-DA uptake and autoradiography, we now report on in vitro neurone-glia interactions and show that glial cells exert a morphogenetic effect on DA neurones. Dopaminergic neurones from the mesencephalon were plated on glial monolayers prepared either from the striatal or the mesencephalic region of the embryonic brain. On mesencephalic glial cells the majority of DA neurones develop a great number of highly branched and varicose neurites, whereas on striatal glia they only exhibit one long, thin and rather linear neurite. These results demonstrate that glial cells from two different brain regions have distinct properties which could be used to define neuronal polarity observed in vivo.

Animals↗
PubMedDate not supplied

[Tolerance and dependence on opioid analgesics: experimental and clinical aspects].

Long-term administration of morphine for chronic non-malignant pain continues to be controversial, mainly because of the fear of opioid addiction and abuse. It is important to distinguish three phenomena: tolerance of the analgesic and side-effects of the drug, physical dependence (which is a pure pharmacological event) and addiction (defined as a compulsive drug-related behaviour). Animal studies suggest that similar mechanisms underlie tolerance and physical dependence. These may result from an imbalance between anti- and pro-nociceptive mechanisms. By contrast, the occurrence of an addictive behaviour depends on both different endogenous mechanisms and environmental factors. Clinical data suggest that the use of stable doses of morphine (or other opiates) is common in patients suffering from chronic non-malignant pain. However, drug addiction might develop in 'at-risk patients' and therefore the decision to start long-term treatment with an opiate should be undertaken very cautiously, and ongoing assessment of aberrant drug-related behaviours should be undertaken repeatedly.

Analgesics, Opioid↗