Michel Delaage

Immunohistochemical localization of dopamine in the brain of the insect Locusta migratoria migratorioides in comparison with the catecholamine distribution determined by the histofluorescence technique

SummaryAs part of a follow-up study to our previous investigation of the catecholaminergic neurosecretory cells in the brain of adult female locusts (Locusta migratoria migratorioides) by means of the formaldehyde-induced fluorescence method, we have attempted to specify the identity of the amines present in these cells by an immunohistological technique. Using a recently developed anti-dopamine serum, we have demonstrated that the majority of the cate cholaminergic median neurosecretory cells contain dopamine. Moreover, dopamine is present in some cell bodies of other zones of the brain, i.e. the median subocellar neurosecretory cells, perikarya in external areas of the protocerebrum, below the calyces, around the pedunculus, in the optic lobes (between the lobula and the medulla, between the medulla and the lamina), and in external zones of the tritocerebrum. Among the structured neuropils, which were particularly fluorescent in the formaldehyde-induced fluorescence method, only the pedunculus, the posterior part of the central body, the external zones of the α- and β lobes and the proximal part of the lamina contain little dopamine.

Biochemical and Pharmacological Characterization of Serotonin‐O‐Carboxymethylglycyl[125I]Iodotyrosinamide5 a New Radioiodinated Probe for 5‐HT1B and 5‐HT1D Binding Sites

Abstract: There is a lack of radioactive probes, particularly radioiodinated probes, for the direct labeling of serotonin‐1B (5‐HT1B) and serotonin‐ID (5‐HT1D) binding sites. Serotonin‐0‐carboxymethylglycyltyrosinamide (S‐CM‐GTNH2) was shown previously to be specific for these two subtypes; we, therefore, linked a 125I to its tyrosine residue. Biochemical and pharmacological properties of S‐CM‐G[125I]TNH2‐binding sites were studied by quantitative au‐toradiography on rat and guinea pig brain sections. S‐CM‐G[I25I]TNH2 binding is saturable and reversible with a KD value of 1.3 nM in the rat and 6.4 nM in the guinea pig. Binding is heterogeneous, paralleling the anatomical distribution of 5‐HT1B sites in the rat and of 5‐HTD sites in the guinea pig. The binding of 0.02 nM S‐CM‐G[125I]TNH2 was inhibited by low concentrations of 5‐HT, S‐CM‐GTNH2, CGS 12066 B, 5‐methoxytryptamine, and tryptamine in both species. Propranolol inhibited the radioligand binding with a greater affinity in the rat than in the guinea pig. Conversely, 8‐hydroxy‐2‐(di‐n‐propylamino)tetralin inhibited S‐CM‐G[125I]TNH2 binding with a greater affinity in the guinea pig than in the rat. Other competitors, specific for 5‐HT,c, 5‐HT2, 5‐HT3, and adrenergic receptors, inhibited S‐CM‐G[125I]TNH2 binding in rat and guinea pig substantia nigra and in other labeled structures known to contain these receptors, but only at high concentrations. S‐CM‐G[I25I]TNH2 is then a useful new probe for the direct study of 5‐HT1B and 5‐HT1D binding sites.

A novel long-lasting dopamine receptor blocker: haloperidol-bovine serum albumin conjugate.

The present study was undertaken in order to develop a long-lasting antagonist of dopamine receptors with a technique applicable to other molecules. Haloperidol was immobilized on a macromolecular backbone (bovine serum albumin) with a coupling ratio of 14 molecules haloperidol per molecule of bovine serum albumin. The long-lasting blockade of dopamine receptor activity was evaluated with the d-amphetamine-induced rotation model in rats. Unilateral intracerebral infusion of the conjugate into the caudate nucleus induced a blockade of dopamine receptors which lasted more than six days. The conjugate was able to trigger a greater amphetamine-induced rotation rate then haloperidol alone. This ipsilateral rotation appeared after doses of conjugate lower than those needed for unilateral haloperidol intracaudate infusion. This compound will enable the reversible blockade of dopaminergic transmission in a restricted area of the brain (diffusion of the conjugate was studied in detail) over a period of time needed for a behavioural study without the drawbacks of chemical or mechanical lesions.