Biomedical subjects

M J Besson

Publications and source records attributed to M J Besson.

At least 19 recordsLinked to original sources

PubMed1992

Distribution of [3H]clonidine binding sites in the brain of the convulsive mutant quaking mouse: a radioautographic analysis.

The radioautographic analysis of [3H]clonidine binding was performed on brain slices from the convulsive mutant mice quaking and their controls of the same strain. In the quaking mice significant increases were observed mostly in the brainstem and the cerebellum, but also in a few regions of the forebrain, such as the lateral and medial thalamic nuclei, the medial geniculate nucleus, the amygdala and the hypothalamus. Other regions, such as the cerebral cortex and the hippocampus, which are classically involved in various models of epilepsy, but not in the quaking mice, did not show any modification of [3H]clonidine binding. A high degree of correlation was found between the structures with an increased density of alpha 2-adrenoceptor binding sites and the distribution of regions from which seizures can be elicited by intracerebral electrical stimulation in head-restrained quaking mice. This comparison emphasizes the role of noradrenaline acting at the level of alpha 2-adrenoceptors in the epileptic syndrome of the quaking mutants.

Animals↗

PubMed1992

Expression of GAD mRNA in GABA interneurons of the rat medial frontal cortex.

The distribution of glutamic acid decarboxylase (GAD) mRNA containing cells was studied in the rat medial frontal cortex (MFC). The neurons labelled by the 35S-labelled cDNA probe were distributed uniformly throughout all the layers and represented 16% of the total neuronal population. It was possible to distinguish two cell populations expressing high and low levels of GAD mRNA corresponding to 63% and 27% of labelled cells, respectively. Concerning the laminar distribution of these two populations of GAD mRNA containing neurons, no marked difference was observed between the various areas of the MFC.

Animals↗

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

In vivo release of newly synthesized [3H]GABA in the substantia nigra of the rat: relative contribution of GABA striato-pallido-nigral afferents and nigral GABA neurons.

The release of [3H]gamma-aminobutyric acid ([3H]GABA) continuously formed from [3H]glutamine has been measured with a push-pull cannula implanted in the substantia nigra of the rat anesthetized with ketamine. Consistent with the high density of GABA terminals coming from both the striato-pallido-nigral afferents, and from GABA nigrofugal neurons, our results showed that a large amount of [3H]GABA was spontaneously released in the reticulata, about 4 times higher than in the compacta. In the absence of calcium the spontaneous [3H]GABA release was reduced (-30%), as well as the K(+)-induced release of [3H]GABA (-66%). Bicuculline (10(-4) M) did not affect the K(+)-evoked release of [3H]GABA, suggesting that autoreceptors on GABA afferent fibers are distinct from the GABAA subtype. Partial lesions of striato- and pallido-nigral GABA neurons with kainic acid (1.2 micrograms) decrease by 40% the glutamic acid decarboxylase (GAD) activity in the ipsilateral SN without decreasing the spontaneous release of [3H]GABA; even following extensive lesions with kainic acid (2.5 micrograms), GAD activity (-72%) and spontaneous [3H]GABA release (-83%) were not completely abolished. These results suggest that a non-negligible contribution of GABA nigral neurons accounts for the spontaneous GABA release measured in the substantia nigra. This is further supported by the decrease (-20%), and the increase (+40%) of [3H]GABA release produced by the local application of glycine (10(-6) M), and bicuculline (10(-4) M), which respectively, inhibits and activates the nigral neuron activity. The contribution of nigral GABA neurons to the amount of [3H]GABA release from the substantia nigra, is likely linked to their high spontaneous firing rate.

Anesthesia↗

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

Opposing effects of dopamine D2 receptor stimulation on the spontaneous and the electrically evoked release of [3H]GABA on rat prefrontal cortex slices.

The spontaneous and the electrically evoked release of [3H]GABA were studied in vitro on slices of rat medial prefrontal cortex. The slices were preincubated with [3H]GABA and then superfused with a Krebs' solution. The superfusion with a Ca(2+)-free medium progressively increased the spontaneous [3H]GABA release and strongly decreased the electrically evoked release of [3H]GABA (-65%). The effects of three dopaminergic D2 receptor agonists (RU24926, lisuride and LY171555) were studied on both the spontaneous and the electrically evoked [3H]GABA release. The spontaneous release of [3H]GABA was increased by exposure to each of these three D2 agonists. RU24926 produced a dose-dependent increase from 10(-9) to 3 x 10(-8) M and the maximal effect was totally abolished by the dopaminergic D2 receptor antagonist sulpiride (10(-5) M). With lisuride a progressive increase of [3H]GABA release was observed and a plateau value was reached with concentrations between 10(-7) and 10(-6) M. These effects were totally reversed by 10(-5) M sulpiride. The dose-response relation for LY171555 was bell-shaped, with a maximal effect being obtained with 10(-9) M) LY171555. This effect decreased with a higher concentration (10(-8) M) and finally was no longer observed for 10(-7) M LY171555. The maximal increase induced by LY171555 was totally abolished by 10(-5) M sulpiride. In contrast, the electrically evoked release of [3H]GABA was inhibited by these three D2 agonists. The IC50 value of the inhibition was 4.1 x 10(-8) M for RU24926 and 2 x 10(-7) M for lisuride. Sulpiride (10(-5) M) totally abolished the effect of 10(-7) M RU24926. In the concentration range of lisuride examined, a 50% reduction of the lisuride inhibition was obtained in the presence of sulpiride (10(-5) M). The dose-response curve obtained with LY171555 had a U-shape, with a maximal inhibition reached with 10(-8) M, whereas no effect was observed with 10(-6) M. The inhibition induced by 10(-8) M LY171555 was completely antagonized by 10(-5) M sulpiride. The D2 agonist-induced inhibition of the electrically evoked release of [3H]GABA was mimicked by dopamine endogenously released by 10(-5) M amphetamine. This effect was reversed by 10(-5) M sulpiride. Our data provide further evidence for a dopaminergic control of GABA interneurons in the prefrontal cortex. This regulation implies the activation of D2 dopaminergic receptors. The possible mechanisms underlying the opposite effects of D2 agonists on the spontaneous and the electrically evoked release of [3H]GABA are discussed.

Amphetamine↗

PubMed1991

Synergism between D1 and D2 dopamine receptors in the inhibition of the evoked release of [3H]GABA in the rat prefrontal cortex.

In order to examine a possible interaction between D1 and D2 receptors in the dopaminergic control of the electrically-evoked release of [3H]GABA in the rat prefrontal cortex, the effects of D1 and D2 dopamine agonists were studied in vitro on cortical slices. The D1 agonist SKF38393 (10(-5) M) inhibited the electrically-evoked release of [3H]GABA. This effect was totally reversed by both the D1 antagonist SCH23390 (10(-7) M) and the D2 antagonist sulpiride (10(-5) M). We previously observed that maximal D2-mediated inhibition of the electrically-evoked release of [3H]GABA was obtained with 10(-7) M RU24926 and 10(-8) M LY171555. Here we showed that the inhibition produced by these two D2 agonists is also abolished by 10(-7) M SCH23390. In dopamine-depleted slices from reserpine-treated animals, it was not possible to detect an effect of either RU24926 (10(-7) M) or SKF38393 (10(-5) M), suggesting a permissive role of endogenous dopamine in the effect of either D2 or D1 agonist. Finally, SKF38393 used at a subliminar concentration (10(-6) M) was able to potentiate the effect of a liminar concentration of RU24926 (1.5 x 10(-8) M). Taken together these results strongly suggest that in the rat prefrontal cortex a D1-D2 receptor synergism is involved in the dopaminergic control of the electrically-evoked release of [3H]GABA.

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗

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↗

PubMed1990

Anticonvulsant effects of antagonists of the N-methyl-D-aspartate receptor complex in a genetic model of epilepsy: the quaking mouse.

Tonic-clonic convulsions of mutant quaking mice were antagonized by the intracerebroventricular injection of N-methyl-D-aspartate receptor antagonists. The competitive antagonists, CPP (3-((+/-)-2-carboxypiperazin-4-yl)-propyl-1-phosphonic acid) and CGS 19755 (cis-4-(phosphonomethyl)-2-piperidine carboxylic acid), exerted a partial anticonvulsant action, with ED50S of 0.115 and 0.076 nmol, respectively. The non-competitive antagonists, TCP (1-(1-(2-thienyl)cyclohexyl)piperidine) and MK-801 [+)-5-methyl-10,11-dihydro-5H-dibenzo(a,d)cyclohepten-5,10-imine), provided full protection, with ED50s of 4.49 and 2.67 nmol, respectively. The competitive antagonists elicited a marked ataxia whereas the non-competitive antagonists did not have side-effects. These results might reflect the involvement of glutamatergic neurotransmission in the convulsions of the quaking mutants.

Animals↗

PubMed1990

Co-expression of neuropeptides in the cat's striatum: an immunohistochemical study of substance P, dynorphin B and enkephalin.

The expression of tachykinin-like and opioid-like peptides was studied in medium-sized neurons of the caudate nucleus in tissue from adult cats pretreated with colchicine. Two methods, a serial thin-section peroxidase-antiperoxidase technique and a two-fluorochrome single-section technique, were applied. Quantitative estimates were made mainly with the peroxidase-antiperoxidase method. The numbers of neurons expressing substance P-like, dynorphin B-like, and enkephalin-like immunoreactivity were recorded in regions identified, respectively, as striosomes and extrastriosomal matrix. Striosomes were defined by the presence of clustered substance P-positive and dynorphin B-positive neurons and neuropil. Tests for the co-existence of enkephalin-like peptide and glutamate decarboxylase-like immunoreactivity were also made with the peroxidase-antiperoxidase method. Co-expression of substance P-like and dynorphin B-like immunoreactivities was the rule both in striosomes and in the matrix. In striosomes, substance P-like immunoreactivity was found in 96% of dynorphin B-immunoreactive neurons, and in the matrix 89% of dynorphin B-positive cells contained substance P-like immunoreactivity. Substance P/dynorphin B-positive neurons corresponded to over half (57%) of the neurons in striosomes but only 39% of the neurons in the matrix. Both in the matrix and in striosomes, about two-thirds of all neurons (63% and 65%, respectively) were identified as enkephalin-positive. Among all substance P/dynorphin B-positive medium-sized neurons, 76% also contained enkephalin-like antigen. The enkephalin-positive neurons characterized by triple peptide co-existence (enkephalin/substance P/dynorphin B) represented a mean of 63% of striosomal enkephalin-positive neurons (41% of all striosomal neurons) and 35% of matrical enkephalin-positive neurons (26% of all matrical neurons). Finally, nearly all enkephalin-positive neurons were immunoreactive for glutamate decarboxylase, and therefore probably GABAergic, but only about half the glutamate decarboxylase-positive population was enkephalin-immunoreactive. These findings suggest that neuropeptides from three distinct precursors may be co-localized in single medium-sized neurons in the striatum, and that the differential patterns of co-expression of substance P-like, dynorphin B-like, and enkephalin-like peptides may confer functional specializations upon subpopulations of GABAergic neurons giving rise to the efferent projections of the striatum. The linked expression of substance P-like and dynorphin B-like peptides in single neurons both in striosomes and matrix suggests that some regulatory mechanisms controlling peptide expression apply regardless of compartment.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

PubMed1990

[D2 dopaminergic receptor activation enhances the spontaneous release of 3H-GABA in the prefrontal cortex of rats, in vitro. The facilitating role of D1 dopaminergic receptors].

The effects of three D2 dopaminergic agonists on the spontaneous release of 3H-GABA have been studied on rat prefrontal cortical slices. LY171555 (10(-9) M), RU24926 (3 x 10(-8) M) and lisuride (10(-7) M) respectively enhanced the spontaneous release by 25, 20.5 and 23%. These effects were totally reversed by the D2 antagonist sulpiride (10(-5) M). Furthermore, subliminar concentration of RU24926 (10(-9) M) and of the D1 agonist SKF38393 (10(-6) M) induced a clear enhancement of the spontaneous release of 3H-GABA when they were superfused simultaneously. Our results suggest that in the prefrontal cortex, the spontaneous release of 3H-GABA is under an activatory D2 dopaminergic control. The activation of D1 receptors seems to have an enabling effect on this regulation.

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗

PubMed1989

Three-dimensional organization of the striosomal compartment and patchy distribution of striatonigral projections in the matrix of the cat caudate nucleus.

Acetylcholinesterase staining on successive frontal or sagittal sections was used to determine the three-dimensional organization of the striosomal and matrix compartments in the adult cat caudate nucleus. Reconstruction drawings of the acetylcholinesterase-poor zones (striosomes) indicated that the striosomal compartment is a labyrinthine network organized in the rostrocaudal and mediolateral axis which is reproducible from one animal to another. Four main anteroposterior channels converging in the mediorostral pole of the caudate nucleus were distinguished. Seven to eight diagonally oriented channels crossing the previous ones were seen also in the mediolateral axis on the central core of the caudate nucleus. The pattern of organization of the numerous and tortuous striosomal channels was more complicated medially, while the lateral part of the caudate nucleus was represented mainly by the matrix compartment. In addition, a sub-compartmentation of the matrix was demonstrated by retrograde tracing studies made by injecting either horseradish peroxidase-wheat germ agglutinin, [14C]amino acids or a mixture of horseradish peroxidase-wheat germ agglutinin and [14C]amino acids in several areas of the substantia nigra pars reticulata. Labelled patches were seen with both tracers, their topographical localization depended on the nigral injection site but reconstruction analysis indicated that the populations of cells which innervate the substantia nigra pars reticulata originate in the two third lateral parts of the caudate nucleus all along its rostrocaudal extension. Examination of horseradish peroxidase-wheat germ agglutinin labelled cells indicated that not all cells were labelled in patches suggesting a further sub-compartmentation of these patches. Finally, a comparison of the topographical distributions of labelled patches and of striosomes revealed that most patches were located in the extrastriosomal matrix.

Acetylcholinesterase↗

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↗

PubMed1989

Neuroleptic-sensitive binding sites in the nigrostriatal system: evidence for differential distribution of sigma sites in the substantia nigra, pars compacta of the cat.

The sigma site is a recently described binding site to which dextrorotary isomers of certain psychotomimetic benzomorphans bind specifically. Classical and nonclassical neuroleptics also have high affinity for the sigma site, including neuroleptics known to bind to the D2 dopamine receptor. The affinity of some D2-binding neuroleptics for the sigma site has raised the possibility that certain important effects of antipsychotic drugs may relate to the sigma site. Left unresolved has been the question of how these actions could relate to dopaminergic systems. To explore this issue we carried out an autoradiographic binding study of the distribution of the sigma-selective ligand 3H-DTG in the nigrostriatal system. We report here that haloperidol-displaceable 3H-DTG binding sites are densely concentrated in an anatomically discrete subdivision of the cat's substantia nigra pars compacta. This zone, identifiable as the striosome-projecting densocellular zone of the pars compacta, also shows heightened D2-related ligand binding but has reduced D1-related ligand binding relative to other parts of the nigral complex. This evidence suggests that sigma-mediated interactions with dopaminergic systems may occur in the substantia nigra pars compacta and that the functional effects of these interactions may influence the nigrostriatal projection to striosomes differentially.

Animals↗

PubMed1988

Topographical organization of efferent projections from the cat substantia nigra pars reticulata.

The topographical organization of the efferent projections from the cat substantia nigra (SN) to the thalamus and the superior colliculus was examined using the anterograde transport of horseradish peroxidase-wheat germ agglutinin (HRP-WGA) and of labelled proteins. HRP-WGA or a mixture of [14C]amino acids was injected into various areas of the SN and the transported material visualized on coronal brain sections by histochemistry or autoradiography, respectively. The retrograde transport of [14C]gamma-aminobutyric acid ([14C]GABA) injected into thalamic nuclei was used also to determine the identity of the nigrothalamic projections. Identical results were found using either the anterograde transport of HRP-WGA or of labelled proteins. In the thalamus, dense nigral projections were observed in the nucleus ventralis medialis (VM) and in the rostromedioventral part of the nucleus ventralis lateralis (VL) whilst more limited projections were seen in the nuclei centralis lateralis (CL) and paracentralis (PC) as well as in the paralamellar zone of the nucleus medialis dorsalis (MD-Il). In addition, a patchy distribution of HRP-WGA or of radioactivity was found in the intermediate layer of the superior colliculus. More precisely, labelling of the VM was dense following injection of [14C]amino acids into the intermediate part of the SN pars reticulata (SNR) regardless of the depth of the injection site, whilst the intralaminar nuclei were labelled preferentially following injections made into the dorsal part of the intermediate SNR. Nigral projections to the intermediate layer of the superior colliculus were visualized over the whole mediocaudal and laterorostral extent when [14C]amino acids were injected into the rostral part of the SNR. Labelling of the superior colliculus was also seen following injection of [14C]amino acids into the intermediate part of the SNR but, in this case, ventral injections led to a more intense labelling than dorsal ones. Both the SNR and the SN pars compacta (SNC) were labelled when [14C]GABA was injected into the VM nucleus of the thalamus, confirming that the nigro VM projection is GABAergic and showing that recurrent collaterals of these GABAergic cells innervating the SNC also contained the transported radioactive material. In this condition ([14C]GABA injection into the VM), the thalamic reticularis nucleus also exhibited a dense labelling.(ABSTRACT TRUNCATED AT 400 WORDS)

Amino Acids↗

PubMed1988

[3H]SCH 23390 binding to D1 dopamine receptors in the basal ganglia of the cat and primate: delineation of striosomal compartments and pallidal and nigral subdivisions.

The distribution of D1 dopamine receptors was studied autoradiographically in the basal ganglia of the cat, monkey and human. These receptor binding sites were labeled directly with the D1-selective antagonist [3H]SCH 23390, and ligand-binding assays were performed concurrently. Serial- or same-action analysis permitted comparisons among D1 binding distributions, acetylcholinesterase staining and tyrosine hydroxylase immunoreactivity. In all species studied, the dorsal striatum exhibited patches of particularly dense D1 binding in correspondence with acetylcholinesterase-poor striosomes. Highly patterned binding was present in the ventral striatum. Distinctions in binding density were observed among the subdivisions of the globus pallidus and of the substantia nigra. The external segment of the pallidum was extremely sparse in D1 binding, whereas the internal segment (or entopeduncular nucleus in the cat) was a site of high D1 binding density. The binding density was greatest in the core of the internal segment, and tyrosine hydroxylase-positive fibers surrounded and weakly dispersed themselves through this core. Weak binding was present in the ventral pallidum. In the substantia nigra, the pars reticulata demonstrated the densest binding, particularly medially. The pars compacta showed much sparser binding, though some of its tyrosine hydroxylase-positive neurons had dendrites extending ventrally into the zone of dense D1 binding in the pars reticulata. We conclude that [3H]SCH 23390-defined D1 binding is compartmentalized in the dorsal striatum and that, particularly in relation to the reported distributions of striatal D2 dopamine receptors, this is likely to be of functional significance in the dopaminergic modulation of intrastriatal neurotransmission as well as of afferent and efferent neurotransmission. The segregated localizations of D1 receptors in the substantia nigra suggest predominant activation of the pars reticulata, including ventral and medial regions adjacent to the densocellular zone. Specific pathways from compartments in the striatum to subdivisions of the pallidum may also be differentially modulated by dopamine acting via distinct receptor subtypes. At the level of the pallidum, such D1 modulation appears to be restricted to the internal segment, which projects to the thalamus, rather than to the external pallidum, which projects to the subthalamic nucleus.

Acetylcholinesterase↗

PubMed1987

The role of dopamine released from distal and proximal dendrites of nigrostriatal dopaminergic neurons in the control of GABA transmission in the thalamic nucleus ventralis medialis in the cat.

Halothane-anaesthetized cats implanted with push-pull cannulae were used in this study. Amphetamine was applied in the pars reticulata or pars compacta of the substantia nigra in order to determine the role of dopamine released from distal or proximal dendrites of dopaminergic cells in the control of GABAergic transmission in the nucleus ventralis medialis of the thalamus. When applied for 30 min in either the pars reticulata or the pars compacta, amphetamine (10(-6) M) enhanced to a similar extent the local release of [3H]dopamine synthesized from [3H]tyrosine, these effects being seen mainly during the drug application. The amphetamine-evoked release of dopamine in the pars reticulata produced a long lasting reduction in the release of [3H]GABA synthesized from [3H]glutamine in the nucleus ventralis medialis as well as in the paralamellar zone of the nucleus ventralis lateralis. Opposite effects were observed when amphetamine (10(-6) M) was applied in the pars compacta. In complementary experiments, single unit recordings were made in the intermediate part of the pars reticulata, some of the cells being identified by antidromic activation from the nucleus ventralis medialis. Whether applied in the pars reticulata or pars compacta, amphetamine (10(-6) M, 10 min) evoked a reversible decrease in the firing rate of most recorded cells whether or not they were identified as projecting to the nucleus ventralis medialis. Therefore, the decreased release of [3H]GABA in the nucleus ventralis medialis seen following application of amphetamine in the pars reticulata of the substantia nigra could result from an inhibition of nigrothalamic GABAergic neurons. Since the nucleus ventralis medialis is also innervated by GABAergic neurons originating in the entopeduncular nucleus, single unit recordings were made from cells in this nucleus during the application of amphetamine (10(-6) M, 10 min) into the pars compacta of the substantia nigra, some of which were identified antidromically as projecting to the nucleus ventralis medialis. Most cells identified or not were found to be activated during this treatment. These results suggested that the increased release of [3H]GABA seen in the nucleus ventralis medialis following application of amphetamine in the pars compacta of the substantia nigra might be linked to the enhanced firing rate of entopeduncular-thalamic GABAergic neurons.

Action Potentials↗

PubMed1986

Enhancement of glutamate release in the rat striatum following electrical stimulation of the nigrothalamic pathway.

The release of unlabelled amino acids and newly synthesized [3H]dopamine was estimated in the striatum of halothane-anaesthetized rats superfused using a push-pull cannula. Electrical stimulation of the substantia nigra pars reticulata (SNR), enhanced the release of glutamate (maximal effect +51%) in the ipsilateral striatum. The outflow of [3H]dopamine, aspartate, serine and glutamine was unchanged. Seven-12 days after electrolytic lesion of the ipsilateral ventromedial nucleus of the thalamus SNR, stimulation no longer increased the striatal release of glutamate. It is suggested that electrical stimulation of the SNR enhances the striatal release of glutamate, presumably originating from corticostriatal fibres, by activating a nigrothalamocortical polysynaptic pathway.

Animals↗