PubMed Health⌕ Search

Biomedical subjects

J M Studler

Publications and source records attributed to J M Studler.

18 recordsLinked to original sources
PubMed1988

Lesion of dopaminergic terminals in the amygdala produces enhanced locomotor response to D-amphetamine and opposite changes in dopaminergic activity in prefrontal cortex and nucleus accumbens.

In a previous study using differential pulse voltammetry we demonstrated an interaction between dopaminergic activity in the amygdala and the nucleus accumbens. In the present study, by post-mortem biochemical measurements, we showed that bilateral 6-OHDA lesions of DA innervation of the amygdala leads to an increase in DA activity in the nucleus accumbens (DOPAC/DA ratio +24%) and a reduction (DOPAC/DA ratio -40%) in the prefrontal cortex. In addition, after these lesions in the amygdala, there was an increased behavioral sensitivity to D-amphetamine, demonstrated by enhanced locomotor activity. Increased understanding of the interregulations between dopaminergic activity in forebrain structures may help explain forebrain functions and/or dysfunctions.

Amygdala↗
PubMed1988

Behavioural deficits induced by an electrolytic lesion of the rat ventral mesencephalic tegmentum are corrected by a superimposed lesion of the dorsal noradrenergic system.

The bilateral electrolytic lesion of the ventral mesencephalic tegmentum (VMT) induces, in the rat, behavioural deficits such as locomotor hyperactivity and disappearance of spontaneous alternation ('VMT syndrome'). When a specific 6-hydroxy dopamine (6-OHDA) destruction of the dorsal noradrenergic (NA) ascending pathway was superimposed to an electrolytic lesion of the VMT, animals recovered a normal locomotor activity and the possibility to alternate. Since many studies indicate that the development of the 'VMT syndrome' is linked to the disruption of the dopaminergic (DA) meso-cortico-limbic transmission, it is proposed that the recovery observed is due to an interaction between NA and DA ascending systems in cortical and/or subcortical structures; noradrenergic innervation would have a permissive role on the expression of the 'VMT syndrome', possibly via a mechanism of heteroregulation of DA receptors by NA fibers.

Animals↗
PubMed1988

Extensive co-localization of neurotensin with dopamine in rat meso-cortico-frontal dopaminergic neurons.

In mammalian brain, dopaminergic (DA) cell bodies located in the ventral mesencephalon give rise to meso-cortical, meso-limbic and meso-striatal systems. Among these, the meso-cortical DA pathway is particularly involved in the processing of emotional and cognitive responses. We demonstrate that the rat meso-cortical neurons specifically contain, in addition to DA, another transmitter, Neurotensin. If this co-localization exists in man, it may provide an anatomical substratum for the biological theory of schizophrenia as well as an indication that potential anti-psychotic drugs which act differentially on the DA ascending transmissions can be developed.

Animals↗
PubMed1987

Immunochemical and biochemical characterization of gastrin/cholecystokinin-like peptides in Palaemon serratus (Crustacea Decapoda): intermolt variations.

Gastrin/cholecystokinin (G/CCK)-like peptides cross-reacting with an antiserum specific for the carboxyamide terminal pentapeptide of gastrin and CCK have been detected in the eyestalks and in the stomach of the prawn Palaemon serratus using immunocytochemical methods. In the eyestalks, immunoreactivity is present in the neuroendocrine cells, the X organ-sinus gland tractus and the neurohemal organ itself. This suggests, for the first time, the existence of a neuroendocrine secretion of G/CCK-like peptides. Hemolymph G/CCK level is about 18 pM. In the stomach, G/CCK-like material has been observed in epithelial cells in the cuticle and in the lumen. Molecular sieving of crude extracts of the medulla terminalis from the eyestalks, the stomach, and the hemolymph samples on a Sephadex G-50 filtration column exhibited a molecular heterogeneity of the G/CCK immunoreactive material. Large components were observed principally in the medulla terminalis and in the hemolymph, and smaller forms in the stomach. A fraction common for the three tissues had an apparent molecular weight of 2500 Da. That fraction was characterized further by HPLC and shown to be more hydrophobic than human G17 I. By radioimmunoassay relatively low levels were detected in all the aforementioned organs. Although the concentration of the G/CCK-like components varies during the intermolt cycle, this was the case mainly in the hemolymph and in the stomach. These observations suggest a possible role of G/CCK-like peptides in molting processes.

Animals↗
PubMed1986

Partial protection by desmethylimipramine of the mesocortical dopamine neurones from the neurotoxic effect of 6-hydroxydopamine injected in ventral mesencephalic tegmentum. The role of noradrenergic innervation.

As shown in the rat by estimation of dopamine (DA) and noradrenaline (NA) levels, bilateral 6-hydroxydopamine (6-OHDA, 4 micrograms/microliter) lesions made in the ventral mesencephalic tegmentum (VMT) destroy both ascending DA and NA neurones. Pretreatment of rats with desmethylimipramine (DMI, 30 mg/kg, i.p.), 30 min before microinjection of 6-OHDA into the VMT partially prevented the destruction of the DA neurones innervating the prefrontal and cingulate cortices but not those innervating subcortical structures (nucleus accumbens, olfactory tubercles, septum). Results obtained from the prefrontal cortex of rats with extensive lesions of the ascending NA neurones performed 15 days prior to the 6-OHDA lesions of the VMT in the presence of DMI, imply that NA innervation of the VMT seems to be required for DMI to protect the cortical DA neurons from the neurotoxic effect of 6-OHDA.

Animals↗
PubMed1986

Opposite effects of sulfated cholecystokinin on DA-sensitive adenylate cyclase in two areas of the rat nucleus accumbens.

The nucleus accumbens of the rat receives a mixed DA/CCK8 innervation in its posterior part while its anterior part is innervated by distinct DA and CCK8 fibres. In vitro, the addition of CCK8 (0.3-1 microM) potentiated the activating effect of DA (10-30 microM) on adenylate cyclase in tissue homogenates obtained from the posterior part of the nucleus accumbens, whilst this activating effect was reduced by CCK8 in the anterior part. These results suggest the existence of two types of regulation of the D1 receptor by CCK8 depending on the identity (mixed or not mixed) of their innervating fibres.

Adenylyl Cyclases↗
PubMed1986

Dopaminergic control of 125I-labeled neurotensin binding site density in corticolimbic structures of the rat brain.

In the rat brain, destruction of dopaminergic cell groups by injections of 6-hydroxydopamine into the ventral mesencephalic tegmentum results in large decreases in the number of neurotensin binding sites in the mesencephalon and the striatum. In contrast, these lesions produce an increase in the number of 125I-labeled neurotensin binding sites in the lateral part of the prefrontal cortex despite a large decrease in cortical dopamine levels. Increases in the number of 125I-labeled neurotensin binding sites in this cortical area as well as in the entorhinal cortex, the nucleus accumbens, and the central part of the striatum were also obtained after chronic blockade of dopamine neurotransmission by a long-acting neuroleptic pipotiazine palmitic ester. We propose that dopamine inputs regulate the density of postsynaptic neurotensin binding sites through cortical and subcortical dopamine receptors. Therefore, some of the clinical effects of neuroleptics in schizophrenic patients could be partly related to changes in neurotensin neurotransmission.

Animals↗
PubMed1986

Contribution of noradrenergic neurons to the regulation of dopaminergic (D1) receptor denervation supersensitivity in rat prefrontal cortex.

3,4-Dihydroxyphenylethylamine (DA, dopamine) levels in the rat prefrontal cortex were selectively decreased by 52%, leaving noradrenaline (NA) levels unaffected, 4 weeks following restricted bilateral electrolytic lesions of the ventral mesencephalic tegmentum (VMT). These lesions also induced a significant increase in DA-sensitive, but not isoproterenol-sensitive, adenylate cyclase activity in tissue homogenates (+38%). We had shown previously that chemical (6-hydroxydopamine, 6-OHDA) lesions of the VMT destroy both ascending DA and NA fibers but do not alter the D1-receptor density in the prefrontal cortex. In this study, electrolytic lesions of the VMT were combined with bilateral injections of 6-OHDA made laterally in the pedunculus cerebellaris superior to assess the role of NA fibers in the development of D1-receptor supersensitivity. This combined treatment produces a large decrease of cortical NA levels (-95%), an increase in beta-adrenergic-sensitive adenylate cyclase activity (+110%), and a decrease in DA levels (-60%), but does not alter D1-receptor density in the prefrontal cortex. These results indicate that the development of D1-receptor supersensitivity in the prefrontal cortex following electrolytic lesion of the VMT depends on the presence of an intact NA innervation.

Adenylyl Cyclases↗
PubMed1984

Non-DA prefronto-cortical efferents modulate D1 receptors in the nucleus accumbens.

Bilateral injections of 6-OHDA in the ventral mesencephalic tegmentum (VMT) destroy the DA afferents of the nucleus accumbens but do not induce any denervation supersensitivity of the D1 receptors in the nucleus accumbens. Because other non-DA afferent fibers might also regulate D1 receptors in that structure, bilateral ablations of the prefrontal cortex were performed. This lesion induced a 55% decrease of [3H]glutamic acid high-affinity uptake activity in the nucleus accumbens. When the prefronto-cortical ablation was performed simultaneously with the bilateral injection of 6-OHDA in the VMT, a marked hypersensitivity of DA-sensitive adenylate cyclase activity was observed in the nucleus accumbens (+52% increase of Vmax and a two-fold decrease of the Kapp for DA) while the ablation of the prefrontal cortex alone induced only a +14% (P less than 0.01) increase of D1 receptors in that structure. These results indicate that the regulation of D1 receptors in the nucleus accumbens is not solely dependent on the presynaptic DA innervation and that other non-DA fibers, such as those of the cortico-nucleus accumbens pathway, might contribute to it.

Adenylyl Cyclases↗
PubMed1984

Pharmacological study on the mixed CCK8/DA meso-nucleus accumbens pathway: evidence for the existence of storage sites containing the two transmitters.

The mixed CCK8/DA meso-nucleus accumbens pathway was used as a model to study the effects of some pharmacological treatments on the two coexisting transmitters. Reserpine (7 mg/kg i.p.), which depletes monoamine vesicles, induced as early as 1 h following its injection a selective decrease (36%) of CCK8 levels in the posterior part of the nucleus accumbens, an area innervated by the mixed CCK8/DA projection. In contrast, this treatment was without effect on CCK8 levels in the anterior nucleus accumbens and the ventral striatum, two areas which contain distinct CCK8 and DA innervations. Apomorphine (5 mg/kg i.p.), which is known to inhibit the firing rate of DA cells, did not block the reserpine- induced decrease in CCK8 levels suggesting that reserpine is acting on CCK8 storage. This mechanism of action was further substantiated by results obtained with alpha-methyl-p-tyrosine (alpha-MpT, 200 mg/kg i.p.) since no change in CCK8 levels was observed 4 h after this treatment. However, a selective decrease (35%) in CCK8 levels was found in the posterior part of the nucleus accumbens 20 h after two successive alpha-MpT injections. This suggested that long-term interruption of DA transmission resulted in an activation of CCK8/DA cells leading to a release of CCK8. The partial effect of reserpine on total CCK8 stores in CCK8/DA fibers suggests that the peptide is distributed in two types of storage compartments, one of them being sensitive to reserpine and possibly corresponding to mixed CCK8/DA vesicles.

Animals↗
PubMed1984

Biochemistry of the hypothalamus in Parkinson's disease.

We assayed the content of neurotransmitters (or their synthesizing enzymes) and neuropeptides in the hypothalamus of control and parkinsonian brains post mortem. Only dopamine concentrations were lower than normal in Parkinson's disease, suggesting that deficiency in hypothalamic dopamine transmission may play a role in the autonomic and endocrine abnormalities of this disorder.

Aged↗
PubMed1982

CCK-8-Immunoreactivity distribution in human brain: selective decrease in the substantia nigra from parkinsonian patients.

The regional distribution of immunoassayable CCK-8 was determined in 12 regions of control and parkinsonian human brain, with specific attention to the possible regional coexistence of CCK-8 with dopamine. In Parkinson's disease, CCK-8-I levels were only decreased in the substantia nigra where dopamine cell bodies lie, and not in striatal and corticolimbic dopamine projecting areas. Our results suggest that the major proportion of dopaminergic neurones degenerated in Parkinson's disease may not contain the CCK-8 peptide.

Appetite Depressants↗
PubMed1977

["Beginning and end of dose" dyskinesias caused by L-DOPA].

The four cases of dyskinesia at the "beginning and end of dose" caused by L-Dopa presented in this series were characterized by four essential features: 1) their onset at the beginning and end of the period of effectiveness of a dose of L-Dopa + IDC (benserazide); 2) their ballic and dystonic appearance associated with a reinforcement of Parkinsonian signs; 3) the possibility of their reduction by an increase and fractionning of the daily dose of L-Dopa; 4) the particular nature of the underlying Parkinsonian problem in which they were seen, i.e. the young age at onset of the disease, the severity of akinesia, and the quality of the clinical response to L-Dopa. Thus on the basis of the circumstances of their development, their appearance, and their treatment, such forms of dyskinesia at the "beginning and end of dose" appear to be different from classical "mid-dose" dyskinesia. In addition, they pose a new physiolopathological problem.

Benserazide↗
PubMedDate not supplied

[Abnormal movements caused by L-DOPA in patients with Parkinson's disease: correlation with the plasma concentrations of DOPA and O-methyl-DOPA].

This study involved twleve parkinsonian patients exposed to abnormal movements provoked by L-DOPA. Including six patients with "mid-dose" dyskinesias and six others with "onset and end of dose" dyskinesias, Correlation between the circumstances of onset of abnormal movements and plasma concentrations of DOPA and O-methyl-DOPA, after administration of a dose of L-DOPA + IDC, gave the following results: 1) mid-dose dyskinesias appeared with the highest plasma concentrations of DOPA, at the maximum therapeutic effect; 2) onset and end of dose occurred during rise and fall in plasma levels of DOPA, coinciding with the relief and the reappearance of parkinsonian symptoms respectively; 3) no correlation could be established between plasma concentrations of O-methyl-DOPA and the duration of the period of clinical remission or of abnormal movements. These biochemical data, completed by the neuropharmacological study of one patient with onset and end of dose abnormal movements suggest the predominant role of a disturbance in central dopaminergic mechanisms in the genesis of abnormal movements, whatever their nature.

Dihydroxyphenylalanine↗