Biomedical subjects

J Caboche

Publications and source records attributed to J Caboche.

4 recordsLinked to original sources

PubMed1991

The quaking mouse: an epileptic mutant with alterations affecting the modulatory mechanisms of the NMDA receptor complex.

The binding of [3H]glutamate and of [3H]1-(1-(2-thienyl)cyclohexyl)piperidine [( 3H]TCP) has been examined in the genetically epileptic mutant mouse, quaking. The density of [3H]glutamate binding sites did not differ between the quaking mice and their controls of the same strain. In the absence of exogenous glutamate or glycine, the density of [3H]TCP binding sites was also similar in the two strains. In both the mutants and their controls, exogenously added glutamate, glycine and glutamate plus glycine dose-dependently increased the binding of [3H]TCP. In the 3 conditions, the modulation of [3H]TCP binding was significantly more efficient in the quaking mice than in the controls. Furthermore, in the presence of glutamate (10(-5) M), the increase of the affinity of the ligand for the ion channel binding site was higher in the mutants than in the controls. These results suggest that the modulatory mechanisms of the N-methyl-D-aspartate/ionophore receptor complex might be altered in these mutants. These alterations might be related to the previously observed anticonvulsant properties of NMDA receptor antagonists in the quaking mouse model of inherited epilepsy.

Animals↗

PubMed1991

Comparative development of D1-dopamine and mu opiate receptors in normal and in 6-hydroxydopamine-lesioned neonatal rat striatum: dopaminergic fibers regulate mu but not D1 receptor distribution.

The postnatal development of D1 dopaminergic receptors (D1 receptors) was investigated in the rat striatum in relation to distribution of mu opiate receptor patches and islandic tyrosine hydroxylase (TH)-immunoreactive fibers. The possible influence of dopaminergic (DA) fibers originating from the substantia nigra on the postnatal distribution of striatal D1 and mu receptors was also examined by producing an early 6-hydroxydopamine (6-OHDA) lesion of DA fibers. D1 and mu receptors were labeled with selective ligands: [3H]SCH 23390 and [3H]DAGO, respectively. During the first postnatal week, control rats showed patches of dense D1 binding sites in the entire rostro-caudal extension of the striatum. The localization of D1 receptor patches corresponded to striosomes identified by TH-immunoreactive islands. The striatal distribution of mu receptors was relatively homogeneous at postnatal day 0 (P0) but was clearly patchy at P3-P4. During the second postnatal week the striosomal pattern of D1 binding sites disappeared along a dorso-ventral gradient whereas mu binding sites remained distributed in patches. Densitometric measurements showed that there was a parallel increase of D1 binding sites in both striosomes and the surrounding matrix from P0 to P4. The disappearance of D1 receptor patches observed in the dorsal striatum at P9 was due to a faster increase of D1 binding sites in the matrix than in striosomes between P4 and P9 whereas a significant difference was still observed between these two compartments in the ventral striatum of P9 rats. During the third postnatal week, the density of D1 binding sites still increased but became progressively uniform in the whole striatum. The intrastriatal injection of 6-OHDA in 2-day-old rats produced a local disappearance of TH-immunoreactive fibers in the striatum and a distal degeneration of TH-immunoreactive cell bodies in the substantia nigra. However an early lesion of striatal DA fibers did not modify the pattern of development or the density of D1 binding sites during the postnatal period examined (1 and 3 weeks after the lesion). The distribution of mu receptors was unchanged 1 week after the lesion but showed a clear disorganization 3 weeks after the lesion. We discuss the differential influence of DA fibers on the distribution of D1 and mu receptors in the rat striatum and the possible role of DA in the regulation of the expression of mu receptors.

Animals↗

PubMed1991

Parallel decrease of glutamic acid decarboxylase and preproenkephalin mRNA in the rat striatum following chronic treatment with a dopaminergic D1 antagonist and D2 agonist.

The levels of mRNA encoding glutamic acid decarboxylase (GAD) and preproenkephalin (PPE) were measured by Northern blot analysis, in the dorsal and the ventral part of the striatum, following long-term treatments with drugs acting selectively on D1 or D2 dopaminergic receptors. Chronic injection of the selective D1 antagonist SCH 23390 elicited a significant decrease in level of both GAD and PPE mRNA (-30%) in the dorsal striatum, whereas no significant change was observed in the ventral striatum. Chronic administration of both SCH 23390 and RU 24926, a D2 agonist, decreased the GAD and PPE mRNA levels in the dorsal (-38 and -57%, respectively) as well as in the ventral (-70 and -60%, respectively) striatum. In the ventral striatum the marked reduction of GAD mRNA levels was paralleled by a significant decrease of Vmax values of GAD enzymatic activity (-41%). These results suggest that the decrease in content of both GAD and PPE mRNA, promoted by the chronic blockade of D1 receptors, is mainly due to the action of dopamine acting on unaffected D2 receptors. Indeed, this decrease is further amplified when the D2 agonist and the D1 antagonist are administered together. Our results substantiate further the molecular mechanisms by which dopamine acts on different populations of GABAergic and enkephalinergic neurons in the two striatal regions examined.

Animals↗

PubMed1989

Postnatal evolution of the gamma-aminobutyric acid/benzodiazepine receptor complex in a model of inherited epilepsy: the quaking mouse.

Binding assays of [3H]muscimol and [3H]-flunitrazepam have been performed on brain homogenates of brainstem, cerebellum, and forebrain of genetically epileptic quaking (qk) mutant mice 20, 40, 70, and 90 days old and their corresponding controls of the same strain (C57BL/6J). The endogenous gamma-aminobutyric acid (GABA) content has been determined in various brain regions of 70-day-old qk and control mice. Finally, the behavioral effects of diazepam, of the mixed GABAA/GABAB receptor agonist progabide, and of the selective GABAB receptor agonist baclofen have been assessed in adult qk mutants. Our results strongly suggest a lack of involvement of GABAergic neurotransmission in the inherited epilepsy of the qk mutant mouse.

Aging↗