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PubMed1997

Neurogenesis in the mammalian neostriatum and nucleus accumbens: parvalbumin-immunoreactive GABAergic interneurons.

We study the neurogenesis of a distinct subclass of rat striatum gamma-aminobutyric acid (GABA)ergic interneurons marked by the calcium-binding protein parvalbumin (PV). Timed pregnant rats are given an intraperitoneal injection of bromodeoxyuridine (BrdU), a marker of cell proliferation, on designated days between embryonic day (E) 11 and E22. Birthdate of PV neurons is determined in the adult neostriatum and nucleus accumbens by using a BrdU-PV double-labeling immunohistochemical technique. PV-immunoreactive interneurons of the neostriatum show maximum birthrates (>10% double-labeling) between E14-E17, whereas PV-immunoreactive interneurons of the nucleus accumbens show maximum double-labeling between E16-E19. In the neostriatum, caudal PV-immunoreactive neurons are born before those at rostral levels, and lateral PV-immunoreactive neurons become postmitotic before medial neurons. In the postcommissural striatum, ventral PV-immunoreactive neurons become postmitotic before dorsal neurons. In the precommissural striatum, ventral neurons are born before dorsal neurons laterally, but a dorsoventral gradient is seen medially. At corresponding coronal levels, PV-immunoreactive neurons of the nucleus accumbens are born shortly after PV neurons of the neostriatum. Analysis of BrdU labeling intensity in the nucleus accumbens shows that medium spiny projection neurons of the shell become postmitotic before neurons of the core. Similarly, PV-immunoreactive interneurons of the nucleus accumbens shell are born before PV interneurons of the core. Compared with cholinergic interneurons of the neostriatum, PV-immunoreactive interneurons are born later, but neurogenetic gradients are similar. The period of striatum PV interneuron genesis encompasses the period for somatostatin interneurons, although the latter neurons do not show neurogenetic gradients, possibly due to heterogeneous subtypes. Consideration of basal telencephalon neurogenesis suggests that subpopulations of striatum interneurons may share common neurogenetic features with phenotypically similar populations in the basal forebrain, with final morphology and connectivity depending on local cues provided by the host environment.

Animals↗
PubMed1998

The "neostriatum" develops as part of the lateral pallium in birds.

Telencephalic organization in birds is so unusual that many homologies between avian and mammalian telencephalic areas remain controversial. Particularly contested is the avian "neostriatum," which has historically been homologized to either mammalian striatum, lateral neocortex, or endopiriform claustrum. Because homologies between these adult structures have been so difficult to resolve, we have begun to examine how telencephalic development diverges between birds and other vertebrates. To this end, biotinylated dextran was injected into the lateral telencephalon of chick embryos at 3 d of incubation, and the distribution of labeled cells was examined up to 14 d later. The data show that a definite boundary to cellular migration develops just ventral to the neostriatum between 5 and 8 d of incubation. Labeled polyclones within the neostriatum stretch from the ventricular zone to the brain surface and exhibit an increasingly rostrocaudal orientation as development proceeds. Individual polyclones contribute cells to several of the distinct auditory, visual, somatosensory, and olfactory regions within the neostriatum. A comparative analysis suggests that the avian neostriatum develops from a precursor region that in other vertebrates gives rise to olfactory cortex and, when present, to other components of the piriform lobe, such as the endopiriform claustrum and basolateral amygdala. Conclusions about lateral pallial homologies between birds and mammals remain uncertain, however, primarily because so little is known about the development of the lateral pallium in mammals. This lacuna might be filled by applying to mammals the novel fate-mapping method described in the present paper.

Animals↗
PubMed1988

Identification of synaptic terminals of thalamic or cortical origin in contact with distinct medium-size spiny neurons in the rat neostriatum.

In order to determine what types of neurons in the striatum receive direct synaptic input from corticostriatal and thalamostriatal fibres and whether these afferents converge on individual striatal neurons, double anterograde labelling of axon terminals was combined with Golgi impregnation at both the light and electron microscopic levels. The area of the central neostriatum that receives input from both the parafascicular nucleus of the thalamus and the somatosensory cortex was identified by retrograde transport of a conjugate of horseradish peroxidase and wheat germ agglutinin (HRP-WGA). The same region of the neostriatum was studied in rats that had received multiple electrolytic lesions in the somatosensory cortex and also an injection of HRP-WGA in different parts of the parafascicular nucleus. Sections of this part of the neostriatum were impregnated by the single-section Golgi procedure after revealing anterogradely transported HRP-WGA. Twelve Golgi-impregnated spiny neurons were recovered and examined in the light and electron microscope after gold-toning. Ten of these neurons were typical very densely spiny medium-size neurons and they were all found to receive asymmetric synaptic input on dendritic spines from degenerating corticostriatal boutons. However, even though numerous boutons labelled anterogradely by HRP-WGA from the parafascicular nucleus were found within the dendritic fields of neurons that received cortical input, none of the terminals from the thalamus made synaptic contact with these neurons. Instead, all 96 thalamostriatal boutons studied were found in asymmetric synaptic contact with dendritic shafts of other neurons. Two such neurons that received input from the parafascicular nucleus were Golgi-impregnated and appeared to be medium-size spiny neurons, but they had a lower density of spines than the typical very densely spiny neurons. An independent confirmation that the targets of thalamostriatal neurons originating in the parafascicular nucleus are dendritic shafts was provided by studying the boutons labelled following electrolytic lesioning or injection of the lectin Phaseolus vulgaris-leucoagglutinin (PHA-L) into this nucleus: these boutons were also found to form asymmetric synaptic contacts with dendritic shafts within the neostriatum. It is concluded that although afferents from the somatosensory cortex and from the parafascicular nucleus converge upon the same part of the neostriatum, they probably do not converge upon the same spiny neurons.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1988

Quantitation of nerve terminal populations: synaptic vesicle-associated proteins as markers for synaptic density in the rat neostriatum.

This study has assessed the contributions of the corticostriatal fibers, the ascending striatopetal fibers, and the intrinsic neostriatal neurons to the nerve terminal population found in the rat neostriatum (caudatoputamen). For this purpose, we have analysed the levels of two different synaptic vesicle-associated proteins, synapsin I and protein p38 (also called synaptophysin), in the neostriatum after specific lesions. Our results indicate that 45-50% of the synaptic vesicle proteins in the rat neostriatum derive from the corticostriatal fibers, that approximately 25-30% of the synaptic vesicle proteins are present in kainic acid-sensitive structures, presumably intrinsic terminals and local collaterals, and that ascending fibers contain 20-25% of the vesicle-associated proteins in the neostriatum. These three neuronal populations therefore comprise 95-100% of the synaptic vesicle-associated proteins in the rat neostriatum, and thus make up most of the nerve terminals in this brain region. The results, which are in general agreement with previous morphometric studies on the rat basal ganglia, therefore indicate that nerve terminals in the central nervous system can be quantitated by use of these biochemical nerve terminal markers. The results also indicate that a somewhat higher percentage of neostriatal nerve terminals belongs to the corticostriatal fibers that previously believed.

Animals↗
PubMed1989

Degeneration and graft-induced restoration of dopamine innervation in the weaver mouse neostriatum: a quantitative radioautographic study of [3H]dopamine uptake.

A recently introduced quantitative radioautographic technique was used to characterize the striatal dopaminergic deficit in weaver mutant mice and to evaluate the extent of DA reinnervation resulting from cell suspension grafts of fetal ventral mesencephalic tissue. Brain slices from normal mice and unilaterally grafted weaver mice were incubated in [3H]DA, in the presence of desipramine and pargyline 3-5 months after graft surgery. Semi-thin sections from the fixed and resinembedded slices were subsequently exposed on tritium sensitive film and afterwards dipped in nuclear emulsion for light microscope radioautography. Alternative slices were embedded in Epon for post-embedding tyrosine hydroxylase (TH) immunocytochemistry. The grain density of the film radioautographs matched well the distribution of TH positive fibers. Both methods revealed an almost complete absence of DA axons in the dorsomedial quadrant of the weaver neostriatum and an increasing density of DA innervation towards the ventrolateral areas. In the light microscope radioautographs, only the ventral striatum (i.e. nucleus accumbens and olfactory tubercle) and a narrow ventral and periventricular zone of the caudate-putamen were covered by silver grain clusters typical of DA varicosity labeling. Such labeled varicosities were nevertheless found in reduced numbers the lateral portion of both nucleus accumbens and the olfactory tubercle. The remaining neostriatum was overlaid by diffuse silver grains. suggesting a deficient DA uptake and storage mechanism in the residual DA fibers in this region. Immunocytochemistry using antibodies specific for DA or TH provided further evidence that the residual DA innervation in the weaver neostriatum was biochemically defective. Weaver mice with grafts of ventral mesencephalic tissue in the right neostriatum showed an amphetamine-induced rotational bias to the contralateral side, which was not seen in the sham-operated animals. In contrast to the intrinsic weaver neostriatal DA innervation, DA fibers of graft origin exhibited the normal, clustered type of varicosity labeling. The computerized image analysis of silver grain density in film radioautographs was calibrated by counting these labeled varicosities in selected areas of light microscope radioautographs from the same sections. Results showed a mean DA reinnervation of neostriatal tissue surrounding the graft of about 20%, in some cases up to 80%, of the density seen in wild type mice, with a gradual decrease with distance up to 1-1.4 mm from the graft. The ventral parts of the neostriatum, which contained higher numbers of residual intrinsic DA fibers, were much more sparsely reinnervated than the dorsal and dorsomedial areas.(ABSTRACT TRUNCATED AT 400 WORDS)

Amphetamines↗
PubMed1983

Localization of substance P-like immunoreactivity in neurons and nerve terminals in the neostriatum of the rat: a correlated light and electron microscopic study.

An antiserum, to substance P has been used to study the neostriatum of rats which has received intracerebral injections of colchicine. Both cell bodies and nerve fibres were found to display immunoreactivity. Some of the fibres were swollen and could be traced back to their parent cell body. Examination in the electron microscope of structures that had first been identified in the light microscope showed that there are two different types of substance P-immunoreactive cell body. The first kind (type I) of immunoreactive cell body was of medium size and had a smooth surfaced nucleus. It displayed the ultrastructural features typical of medium-size spiny neurons. Identified axons of type I neurons gave rise to immunoreactive axon collaterals within the neostriatum: boutons along these collaterals were found to form symmetrical synaptic contacts. The second kind (type II) of immunoreactive cell body was also of medium-size and had a round or oval shape, but the nucleus was deeply indented and was surrounded by a thin rim of cytoplasm. Synaptic input to this neuron was sparse and consisted of small boutons that made symmetrical contacts with the perikaryon and proximal dendrites. Many immunoreactive dot-like structures could be seen in the light microscope: upon examination in the electron microscope these were found to be boutons. All fifty-six synaptic boutons that were studied made symmetrical synaptic contacts. These boutons were indistinguishable from the boutons of axon collaterals of identified type I immunoreactive neurons. The most common postsynaptic structures were dendrites, including some dendritic spines, although synapses between immunoreactive boutons and several perikarya, and an axon initial segment were observed. The morphological features of the immunoreactive boutons in the neostriatum were very similar to one type of substance P-immunoreactive bouton in the substantia nigra and to a bouton type in the substantia nigra which is labelled following the anterograde transport of horseradish peroxidase from the striatum. It is suggested that there are two kinds of substance P-containing neurons in the striatum and that one of these is likely to belong to the medium-spiny class. The latter type of neuron is probably the source of the striatonigral substance P-containing projection and of the immunoreactive boutons within the striatum. The finding of substance P-immunoreactive synaptic boutons within the neostriatum provides a morphological basis for the view that substance P might serve as a neurotransmitter in the neostriatum.

Animals↗
PubMed1977

The topographical distribution of serotoninergic terminals in the neostriatum of the rat and the caudate nucleus of the cat.

The topographical distribution of serotoninergic terminals in the neostriatum of the rat and the caudate nucleus of the cat was established owing to the combined use of microdissection techniques and biochemical microassays. The density of 5-HT terminals in various areas of both structures was quantified first by measuring 5-HT levels in microdiscs of frozen tissue. Since the high affinity uptake process for 5-HT appeared undamaged in isotonic homogenates of previously frozen (--5 degrees C) tissues, it was possible to confirm the findings obtained with the measurement of 5-HT levels by also determining 5-HT uptake activity in these microdiscs. However, in the rat neostriatum, but not in the cat caudate nucleus, [3H]5-HT even at a very low extracellular concentration (4.4 -x 10(-8) M) was taken up not only by serotoninergic terminals but also to a significant extent by dopaminergic terminals. In presence of benztropine, this second component was suppressed and [3H]5-HT uptake activity could then be considered as a specific marker of serotoninergic terminals also in the neostriatum of the rat. In both species, 5-HT terminals were mainly localized in the ventrocaudal area of the structure. In this area, 5-HT levels were among the highest values found in the brain (17 ng/mg protein). The density of 5-HT terminals decreased progressively from the acudal to the rostral planes of the neostriatum in rats or the caudate nucleus in cats. The poorest area, i.e. the dorsorostral zone, contained about 4 times less 5-HT than the ventrocaudal zone of the structure. Electrolytic lesion of the dorsalis (B7) and centralis superior (B8) raphe nuclei during early life resulted in a large decrease of 5-HT levels (--90%) in various parts of the neostriatum of adult rats. The present findings might be of interest to further analyze the role of serotoninergic neurons in extrapyramidal functions.

Animals↗
PubMed1990

Elevation of dopamine D2 but not D1 receptors in adult rat neostriatum after neonatal 6-hydroxydopamine denervation.

Monoamine levels and the binding properties of [3H]SCH23390, a D1-specific ligand, and [3H]raclopride, a D2-specific ligand, were measured in the rostal and caudal neostriatum to investigate the fate of dopamine receptors following bilateral cerebroventricular injection of 6-hydroxydopamine in 3-day-old rats. After survival times of 15, 30 or 90 days, measurement of monoamine levels and of [3H]SCH23390 binding were also obtained from the cerebral cortex. At all three survival times, dopamine content was reduced by more than 90% of control values in both the rostral and caudal neostriatum; in cerebral cortex, the dopamine depletion was less profound (80%) and noticeable only after 1 and 3 months. In the rostral but not the caudal neostriatum, serotonin and 5-hydroxyindoleacetic acid concentrations were markedly increased at 1 and 3 months; cortical serotonin also was augmented at 3 months. There were no changes in neostriatal [3H]SCH23390 binding at any of the survival times, but a transient elevation occurred in the cortex at 1 month. In the rostral but not the caudal neostriatum, [3H]raclopride binding showed a slight elevation at 1 month and a further, highly significant increase at 3 months. As measured in individual rats, this increase in [3H]raclopride binding was linearly correlated with the increase in serotonin turnover (ratio of 5-hydroxyindoleacetic acid/serotonin). Such an up-regulation of D2 receptors, restricted to the rostral neostriatum which was also the site of a serotonin hyperinnervation, was probably indicative of a serotonin control on the expression of D2 receptors after dopamine denervation.

Animals↗
PubMed1991

Serotonergic sprouting in the neostriatum after intrastriatal transplantation of fetal ventral mesencephalon.

The sprouting of serotonergic fibers into the neostriatum of 6-OHDA-lesioned rats should be considered, when assessing the functional aspects of ventral mesencephalic grafts. The degree of serotonergic fiber growth into the neostriatum of rats subjected to unilateral 6-OHDA lesions followed by fetal ventral mesencephalic grafts was examined immunohistochemically. As a measure of serotonergic innervation density, the total length of immunoreactive fibers was quantified as percent area. Four weeks after transplantation, there was complete recovery of (+)-amphetamine-induced rotation. All of the ventral mesencephalic grafts contained serotonin-immunoreactive cells, but much fewer in number than the tyrosine hydroxylase-positive cells found in the same grafts. However, there was significant serotonergic hyperinnervation throughout the transplanted neostriatum compared with the control side. The hyperinnervation derived from the grafted neurons was most marked in the dorsal and lateral sectors of the rostral neostriatum. At 24 weeks after transplantation, the implanted neostriatum still showed a dense serotonergic innervation.

Amphetamine↗
PubMed1983

A theory of the functional organization of the neostriatum and the neostriatal control of voluntary movement.

A theory of the intrinsic, functional organization of the neostriatum and the neostriatal control of voluntary movement is presented. The cell types of neostriatum are described in accordance with the classification scheme of Pasik, Pasik and DiFiglia (ref. 204) and their suspected neurotransmitters are identified. The functional relations between the afferent projections to neostriatum and the intrinsic elements of neostriatum are described. A division of the neostriatal efferents into two functional cell systems is conceived, in which one efferent system, the Spiny I cell matrix, is thought to be represented by a lateral inhibitory network comprised of the common Spiny I neurons which inhibit their targets, while another is termed the Spiny II cell cluster and consists of the far less numerous excitatory efferents of neostriatum (the Spiny II cells) and is represented by clusters of neurons, the members of each cluster consisting of one excitatory efferent neuron and three interneurons. The implications of this view for neostriatal input--output relations are discussed, and the theory is developed by reference to a variety of converging lines of empirical evidence, and is used to interpret the effects of various pharmacologic strategies which have been employed to achieve symptom management in disorders of voluntary movement. In the course of this review, there emerges an integrative theory of the principles governing the neostriatal control of voluntary movement.

Afferent Pathways↗
PubMed1986

Distinct sites of functional interaction between dopamine, acetylcholine and gamma-aminobutyrate within the neostriatum: an electromyographic study in rats.

In order to study the functional interaction between dopamine, acetylcholine and gamma-aminobutyrate within the rat neostriatum, we investigated the effect of intrastriatal injection of different drugs acting on these transmitter systems on muscle tone measured as tonic activity in the electromyogram of the gastrocnemius muscle. Bilateral injection of haloperidol (500 ng) into the rostral neostriatum (rostral injection: A8920-9650(46] induced tonic activity in the electromyogram, whereas injection into the intermediate part (intermediate injection; A7020-7890(46] was ineffective. Muscimol (25 ng) induced tonic activity in the electromyogram, when injected into the intermediate part and not into the rostral part, while bethanechol (1 microgram) was effective when injected into either site. Haloperidol-induced tonic activity in the electromyogram was prevented by coadministration of apomorphine (500 ng) or scopolamine (1 microgram), but not of bicuculline (300 ng). Haloperidol-induced tonic activity in the electromyogram was also reduced by subsequent intermediate injection of scopolamine or bicuculline, while apomorphine was ineffective. Tonic activity in the electromyogram induced by rostral injection of bethanechol was prevented by coadministration of scopolamine, but not of apomorphine. Intermediate injection of scopolamine or bicuculline reduced the tonic activity in the electromyogram after rostral or intermediate injection of bethanechol. Tonic activity in the electromyogram induced by intermediate injection of muscimol was prevented by coadministration of bicuculline, but not of scopolamine. Rostral injection of apomorphine or scopolamine failed to alter the tonic activity in the electromyogram induced by intermediate injection of bethanechol or muscimol. These results point to the existence of: a functional interaction between dopamine and acetylcholine in the rostral neostriatum; a functional interaction between acetylcholine and gamma-aminobutyrate in the intermediate neostriatum, and a functional flow of information from the rostral to the intermediate neostriatum.

Acetylcholine↗
PubMed1987

Astroglial response in the excitotoxically lesioned neostriatum and its projection areas in the rat.

The anatomical distribution of the astrocytic glial reactions, following ibotenic acid-induced neuronal degeneration of the neostriatum in the rat, has been studied immunohistochemically using an antibody directed against the astrocytic marker, glial fibrillary acidic protein. The acute astroglial response to the excitotoxic lesion, determined 7 days post lesion, was compared with a sham-operated group and a chronic group that had received the excitotoxic lesion 6 months prior to histological evaluation. Total doses of 16-20 micrograms ibotenic acid injected unilaterally into the head of the neostriatum caused not only a marked neuronal cell loss but was also accompanied by a large increase in the number and size (about 5 times) of glial fibrillary acidic protein-stained astrocytes throughout the neostriatum by 7 days after lesion. Reactive astrocytes were also observed in the major neostriatal projection areas, the globus pallidus and the substantia nigra pars reticulata, at 7 days post lesion, although no neuronal cell loss could be detected in these regions using regular Cresyl Violet staining. Previous studies of lesions identical to the ones used here have shown that globus pallidus and substantia nigra are deafferented as a result of the neostriatal neuronal degeneration. The reactive astrocytes in the striatal projection areas had a 3-5 times larger size than control astrocytes from the same anatomical region. In animals that received a larger dose of ibotenic acid into the neostriatum (25 micrograms), neuronal cell loss was also observed in the neocortex and reactive glial fibrillary acidic-stained astrocytes were found in the entire neocortex of the injected hemisphere. In the chronic group, 6 months after the excitotoxic lesion, the astroglial response was clearly diminished or absent in the major neostriatal projection areas, but was still present within the lesioned neostriatum. The results suggest that focal neuronal destruction can result in widespread astrocytic glial reactions which follow the anatomical connectivity of the lesioned area. This may have implications for the understanding of the multifocal distribution of glial reactions seen in patients with striatal degeneration as a result of Huntington's disease.

Animals↗
PubMed1991

A light and electron microscopical study of enkephalin-immunoreactive structures in the rat neostriatum after removal of the nigrostriatal dopaminergic pathway.

The pattern of enkephalin immunoreactivity was examined in the adult rat neostriatum, at various times after unilateral removal of the nigrostriatal dopamine input by 6-hydroxydopamine injection into the medial forebrain bundle. Animals were examined 12 days, 26 days or 13 months after the lesion. Enkephalin-immunoreactive synaptic boutons (n = 1018) in the control and the dopamine-depleted neostriatum were analysed in the electron microscope. The area of enkephalin-immunoreactive synaptic bouton profiles was significantly larger in the dopamine-depleted neostriatum and this increase was maximal in rats in which the lesion had been made 26 days or 13 months previously (50% increase). The synaptic specializations of these enkephalin-immunoreactive boutons were significantly longer in the neostriatum from the injected side. Dendritic shafts were the principal postsynaptic target of these boutons (67%) but dendritic spines (18%), perikarya (6.5%) and unidentifiable small dendrites or spines (8.5%) were also contacted. The proportions of enkephalin-immunoreactive boutons on the different postsynaptic targets were not altered by the 6-hydroxydopamine lesion. The increase in enkephalin immunoreactivity observed in the dopamine-depleted neostriatum in previous studies may be explained by the increase in the size of enkephalin-immunoreactive synaptic boutons found in the present ultrastructural investigation. The observations do not rule out the possibility that there is also an increase in the number of immunoreactive synaptic boutons, due to, for example, sprouting of the existing enkephalin-containing fibres.

Animals↗
PubMed1991

Role of neostriatum and nucleus accumbens in stepping induced by apomorphine and dexamphetamine.

Systemic administration of apomorphine and dexamphetamine are known to produce circling in rats by changing the functioning of hindlimb stepping and forelimb stepping, respectively. In the present study intracranial injections of the dopamine antagonist sulpiride were used to study the involvement of the neostriatum and nucleus accumbens in these effects. It was found that injections of sulpiride into the neostriatum, but not the nucleus accumbens, dose-dependently (1-20 ng) reduced the number of apomorphine-induced hindlimb doublets without affecting the dexamphetamine-induced forelimb crossing steps. On the other hand, it was found that injections into the nucleus accumbens, but not the neostriatum, reduced the number of dexamphetamine-induced forelimb crossing steps without affecting the apomorphine-induced hindlimb doublets. This effect was not dose-dependent. The data suggest that the neostriatum, but not the nucleus accumbens, is primarily involved in the apomorphine-induced changes in hindlimb stepping, and that the nucleus accumbens, but not the neostriatum, is primarily involved in the dexamphetamine-induced changes in forelimb stepping.

Animals↗
PubMed1999

Dopamine D1 receptor modulation of glutamate receptor messenger RNA levels in the neocortex and neostriatum of unilaterally 6-hydroxydopamine-lesioned rats.

The effect of treatment with the D1 dopamine receptor agonist SKF 38393 on the expression of metabotropic glutamate receptor 1, 3, 4 and 5 receptor subtypes and of the glutamate N-methyl-D-aspartate ionotropic receptor subunits NRI, NR2A and NR2B was analysed using in situ hybridization. We studied the neocortex and neostriatum of normal rats and of rats unilaterally treated with 6-hydroxydopamine, a neurotoxin that, after intracerebral injection into the ventral tegmental area, causes selective degeneration of the ascending dopamine pathway. In the 6-hydroxydopamine-lesioned rats, metabotropic glutamate receptor subtype 3 messenger RNA levels were ipsilaterally increased in the neocortex and neostriatum, while the levels of metabotropic glutamate receptor subtype 4 messenger RNA were bilaterally increased in both regions. When administered to the 6-hydroxydopamine-lesioned rats, the D1 receptor agonist SKF 38393 (3 x 20 mg/kg, s.c.) produced a bilateral decrease in the expression of the metabotropic glutamate receptor subtype 1 and 5 receptor messenger RNA levels in the neocortex and neostriatum. In the neostriatum, SKF 38393 attenuated the ipsilateral increase in the expression of striatal metabotropic glutamate receptor subtype 3 messenger RNA produced by the 6-hydroxydopamine lesion. Furthermore, SKF 38393 produced a bilateral decrease in the levels of NRI receptor subunit messenger RNA and, in contrast, an increase in the striatal NR2B messenger RNA levels. All of these effects were abolished by the D1 receptor antagonist SCH 23360. These results indicate a differential D1 receptor-mediated modulation of the expression of some glutamate receptor subtypes in the neostriatum and neocortex, in agreement with the idea of a functional coupling between dopamine and excitatory amino acid systems in both regions. Thus, pharmacological targeting of excitatory amino acid systems could provide alternative or complementary treatment strategies for diseases involving dopaminergic systems in the striatum (e.g., Parkinson's disease) and cortex (e.g., schizophrenia).

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗
PubMed1979

Autoradiographic study of the development of the neostriatum in the rabbit.

Autoradiographic labelling has been employed to analyze the morphogenesis of the neostriatum. Pregnant rabbits received a single intraperitoneal injection of tritiated thymidine at different stages of gestation. Careful microscopical observation of the autoradiographs shows that cellular components of the neostriatum originate between days 15 and 18 of the intrauterine life from a layer of proliferating matrix cells that lies on the floor of the anterior part of the lateral ventrical (ganglionic eminence). From this proliferating layer, precursor cells migrate outwards to reach the developing neostriatum in a sequential fashion according to two gradients of histogenesis. Thus, it was found that neurons formed at early stages occupy a ventromedial position in the neostriatum, while those formed at later stages occupy a dorsolateral position (ventromedial to dorsolateral gradient). Furthermore, the present study indicates that the rostral regions of the neostriatum arise somewhat later than the caudal ones, demonstrating the existence of a caudocephalic gradient of cytogenesis.

Animals↗
PubMed1975

Amphetamine: evaluation of d- and l-isomers as releasing agents and uptake inhibitors for 3H-dopamine and 3H-norepinephrine in slices of rat neostriatum and cerebral cortex.

Release of 3H-doapamine or of 3H-norepinephrine and inhibition of accumulation of 3H-dopamine or 3H-norepinephrine by d- and l-amphetamine were studied in slices of rat neostriatum and in slices of rat cerebral cortex. The two stereoisomers of amphetamine were equally potent as inhibitors of accumulation in the cortex, whereas d-amphetamine was approximately 3-fold more potent than l-amphetamine in the neostriatum. A similar relationship was observed between the two stereoisomers in release experiments. Some spontaneous efflux of 3H-dopamine from tissue slices was evident in absence of added drug in release experiments. When cocaine (2 X 10(-5) M), a known inhibitor of biogenic amine uptake, was added to the medium, there was very little increment in spontaneous efflux of 3H-dopamine in neostriatal slices, but cocaine blocked the release caused by d-amphetamine. This showed that the apparent releasing action of d-amphetamine in the neostriatum was not due to blockade of reuptake of spontaneously released material and that d-amphetamine itself must be taken up to evoke a releasing action. Experiments were designed to compare directly the releasing and uptake inhibiting actions of d-amphetamine. In the cortex, uptake inhibition of 3H-norepinephrine was greater than release over a wide concentration range, while in the neostriatum the two actions were essentially identical in magnitude for 3H-dopamine. We conclude that in the cortex, d-amphetamine can act both to release and to block uptake of 3H-norepinephrine. In the neostriatum, on the other hand, there is releasing action of 3H-dopamine by d-amphetamine (which is stronger than that in the cortex), but the apparent blockade of "uptake" is of questionable significance and appears to result from the release of previously accumulated 3H-dopamine

Amphetamine↗
PubMed1976

Free and conjugated dihydroxyphenylacetic acid: effect of alterations in impulse flow in rat neostriatum and frontal cortex.

Stimulation of the nigro-neostriatal dopamine pathway results in an accumulation of both free and conjugated dihydroxy-phenylacetic acid (DOPAC) in the rat neostriatum. Drugs which have previously been shown to alter impulse flow in central dopaminergic neurons also produce predictable changes in the levels of both free and conjugated DOPAC in both the neostriatum and, in most cases, in the frontal cortex. Drugs such as the antipsychotics which increase impulse flow in the nigro-neostriatal dopamine neurons increase both free and conjugated DOPAC levels in both the neostriatum and frontal cortex. Drugs which reduce impulse flow, such as d-amphetamine and apomorphine, cause a reduction in free DOPAC in both the neostriatum and frontal cortex but reduce DOPAC conjugate only in the neostriatum. Pargyline, a monoamine oxidase inhibitor, causes an extensive depletion of free and conjugated DOPAC in both the striatum and frontal cortex, indicating that these metabolites are rapidly cleared from both of these brain areas.

3,4-Dihydroxyphenylacetic Acid↗