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B Bloch

Publications and source records attributed to B Bloch.

At least 55 records · Page 3Linked to original sources
PubMed1997

Dopamine-adenosine interactions in the striatum and the globus pallidus: inhibition of striatopallidal neurons through either D2 or A2A receptors enhances D1 receptor-mediated effects on c-fos expression.

D1 receptors located on striatonigral neurons and D2 receptors located, together with A2A receptors, on striatopallidal neurons are known to interact functionally. Using in situ hybridization, we examined the effects of D1 and D2 agonists and of an A2A antagonist on c-fos mRNA in identified striatal neurons and in globus pallidus. The full D1 agonist, SKF 82958 (1 mg/kg), induced a homogenous increase of c-fos mRNA in the striatum. This increase occurred to a similar extent in D1 and D2 receptor-containing striatal neurons. Conversely, the D2 agonist, quinelorane (2 mg/kg), decreased c-fos mRNA in these populations but increased it in globus pallidus. The adenosine A2A receptor antagonist, SCH 58261 (5 mg/kg), also decreased c-fos mRNA in D2 receptor-containing neurons in striatum but did not affect pallidal c-fos mRNA. Concomitant administration of either D1 plus D2 agonists or D1 agonist plus A2A antagonist caused a potentiation of c-fos mRNA in striatal neurons expressing the D1 receptor and in globus pallidus. However, only the combination of D1 and D2 agonists modified the c-fos mRNA expression to a "patchy" distribution. Our data show that (1) c-fos expression can be activated through D1 and inhibited through A2A or D2 receptors in both striatal output pathways in normal rats, and (2) D2 receptor stimulation as well as A2A receptor blockade can interact with D1 receptor activation to potentiate c-fos expression in the striatum and the globus pallidus. The data also suggest that the topological alteration of c-fos expression after coadministration of D1 and D2 agonists involves D2 receptors located on interneurons or presynaptically on dopaminergic nerve terminals.

Adenosine↗
PubMed1997

Molecular anatomy of the development of the human substantia nigra.

A series of 15 fetal and perinatal human brains (from week 12 of fetal life to day 2 after birth) was studied in order to describe the anatomical and molecular correlates of the substantia nigra ontogeny. In situ hybridization, immunohistochemistry and binding studies were used to detect D2 dopamine receptor (D2R) mRNA, D2R binding sites, dopamine membrane transporter (DAT) mRNA, tyrosine hydroxylase (TH) protein D1 dopamine receptor (D1R) protein and D1R binding sites. Dopaminergic (DA) neurons of the substantia nigra were detected through TH immunoreactivity from week 12. At week 16, the substantia nigra was clearly delineated as a compact group of intermingled neurons and fibers. From week 19, groups of DA neurons were segregated from the pars reticulata. These groups have been divided into the substantia nigra pars compacta, the ventral tegmental area and the retrorubral area. The DA neurons exhibited a gradual increase in size and branching development until birth. From week 12 onward they expressed several other markers of dopamine transmission, i.e., D2R mRNA, D2R binding sites and DAT mRNA. The ventral tegmental area expressed lower levels of mRNA for DAT and D2R than the pars compacta. From week 12, D1R immunoreactivity and D1R binding sites were also present in the substantia nigra pars reticulata. This suggests that projecting striatonigral neurons, known to express the D1R gene, have developed pathways connecting with the substantia nigra by week 12. Our results demonstrate that the developing substantia nigra in human displays early transcriptional and translational activity for the main constituents of dopaminergic transmission from week 12 and receives at this time dopaminoceptive inputs bearing D1 receptors from the striatum.

Biomarkers↗
PubMed1997

Distribution of NGF receptors in normal and pathologic human lymphoid tissues.

To identify nerve growth factor (NGF) target cells in normal and pathologic human lymphoid tissues, we have studied the expression of the low-affinity NGF receptor (p75LNGFR) and the high-affinity tropomyosin-related kinase NGF receptor (TrkA). A RNAse protection assay revealed the expression of trk transcripts in thymus, spleen, palatine tonsils and lymph nodes. TrkA immunoreactivity was shown in thymic epithelial cells, cryptic tonsillar epithelium and several monocyte-derived cells including epithelioid and multinucleated Langhans' cells, follicular dendritic cells and interdigitated reticular cells. TrkA immunoreactivity was rarely observed in normal T- and B-lymphocytes, but was intense in lymphoma cells of several B-cell lymphoma subtypes, anaplastic large cell lymphomas and Reed-Sternberg cells. Western blot analysis revealed the presence of p75LNGFR and of p80Trk and glycosylated Trk isoforms (gp110, gp140). p75LNGFR immunoreactivity was detected in epithelial Hassal's bodies, follicular dendritic cells, interdigitated reticular cells, periarteriolar macrophages, endothelial sinusal cells and nerve endings. The broad expression of NGF receptors may be an indicator of neurotrophin activity in lymphoid tissues and suggests their implication in inflammatory or lymphoproliferative disorders.

Antibodies, Monoclonal↗
PubMed1997

Ontogeny of the striatal neurons expressing the D2 dopamine receptor in humans: an in situ hybridization and receptor-binding study.

D2 dopamine receptor (D2R) gene expression was analyzed by in situ hybridization and D2R ligand autoradiography in the human striatum during ontogeny. D2R mRNA and ([3H]YM-09151-2)-binding sites were detected in the striatum from week 12 of fetal life. At this time, D2R mRNA and binding sites were predominant in the putamen and occurred in a pattern of clusters. D2R-binding sites displayed a similar pattern. The signal in the caudate nucleus was weak from weeks 12 to 16. From week 20 of fetal life, D2R mRNA and D2R-binding sites signals became intense in the ventral striatum. At birth, D2R mRNA became homogeneously distributed while D2R-binding sites kept an heterogeneously distribution. Comparative topological and temporal analysis of the D2R, enkephalin and D1 dopamine receptor (D1R) mRNAs showed a distinct developmental pattern for each mRNA. Before birth, the neurons expressing enkephalin and D1R mRNAs were preferentially distributed in the matrix and in the striosomes, respectively, while the neurons expressing D2R mRNA did not display a preferential localization. At birth, high levels of enkephalin mRNA were restricted to the matrix; D1R mRNA level was homogeneous throughout the striatum. D2R mRNA was heterogeneously distributed in the whole striatum with high signals located both in the striosomes and the matrix. These results demonstrate that functional D2R are expressed as early as week 12 in the striatum with a heterogeneous distribution. Our findings also demonstrate that, in contrast to what was expected from similar studies in rodents, D2R mRNA and enkephalin mRNA do not display identical, overlapping expression patterns in striatal neurons during human ontogeny.

Corpus Striatum↗
PubMed1997

Cellular expression of adenosine A2A receptor messenger RNA in the rat central nervous system with special reference to dopamine innervated areas.

The cellular distribution of adenosine A2A receptor messenger RNA in the central nervous system was investigated using in situ hybridization with ribonucleotide probes. A specific expression was found in the dorsal (i.e. caudate putamen) and ventral (i.e. nucleus accumbens and olfactory tubercle) striatum, the lateral septum and in some cerebellar Purkinje cells. Simultaneous detection of radioactive and non-radioactive probes showed that the majority of adenosine A2A receptor messenger RNA-containing neurons in the dorsal and ventral striatum co-expressed dopamine D2 receptor messenger RNA and preproenkephalin A messenger RNA. However, a minor sub-population of neurons expressing adenosine A2A receptor messenger RNA, but not preproenkephalin A messenger RNA, was found in clusters along the ventral border of the nucleus accumbens. Only a small number of striatal neurons expressing dopamine D1 receptor or substance P messenger RNAs also expressed adenosine A2A receptor messenger RNA. Finally, in the ventral part of nucleus accumbens and in the olfactory tubercle a major sub-population of neurons expressed preproenkephalin A messenger RNA, but not adenosine A2A receptor messenger RNA. Cholinergic interneurons did not express adenosine A2A receptor messenger RNA. Thus, the extensive co-localization of adenosine A2A and dopamine D2 receptors previously described in the dorsal striatum extends into its ventral part. There is also a high degree of co-expression of adenosine A2A receptor messenger RNA and preproenkephalin A messenger RNA in the ventral striatum, but within this region several topologically defined sub-populations of neurons express only one of these transcripts. A majority of the adenosine A2A receptor messenger RNA-containing neurons in the lateral septum did contain preproenkephalin A messenger RNA, whereas only a few co-expressed dopamine D2 receptor messenger RNA. This detailed investigation demonstrates that most of the subcortical areas innervated by dopamine have an abundant, although restricted expression of the adenosine A2A receptor gene and that this receptor is expressed in very few cells outside these areas. These results predict that adenosine A2A receptors are involved not only in motor behaviour, but also in goal-oriented behaviours.

Adenosine↗
PubMed1997

Possible mechanisms inducing granule cell dispersion in humans with temporal lobe epilepsy.

The stratum granulosum (SG) of the fascia dentata from 17 human epileptic hippocampi was assessed in terms of width, volumetric cell density (VCD) and percentage of cell loss to study the granule cell dispersion (GCD) phenomenon described by Houser. GCD was considered when three conditions were observed, the SG was wider than 120 microns, granule cell (GC) somata did not remain in close apposition to one another the normal clear boundary between the molecular layer and the SG was not maintained. GCD involved a partial zone of the SG in six cases and the whole SG in two cases. Dynorphin mRNA in-situ hybridization was performed in two cases and allowed us to affirm that dispersed cells are actually GC. A close correlation linked GCD, GC loss and VCD decrease in diffuse CA4, laminated CA4, CA3, CA2 and CA1. The discussion is focused on the possible causes of dispersion. Some arguments did not suggest for a migration arrest during development. Nevertheless, in one case, a cluster of horizontal cells in the inner part of the molecular layer could evoke the persistence of normally transient cells during ontogenesis. A neo-migration due to permissive phenomenon induced by gliogenesis, mossy fibers sprouting in the supra-granular layer and over-expression of growth factors is suggested from experimental data. Nevertheless a straining due to the tissue shrinkage observed in severe hippocampal sclerosis (HS) could also be involved in the origin of GCD.

Adolescent↗
PubMed1997

An mRNA encoding a putative GABA-gated chloride channel is expressed in the human cardiac conduction system.

GABA-gated chloride channels are the main inhibitory neurotransmitter receptors in the CNS. Conserved domains among members of previously described GABAA receptor subunits were used to design degenerate sense and antisense oligonucleotides. A PCR product from this amplification was used to isolate a full-length cDNA. The predicted protein has many of the features shared by other members of the ligand-gated ion channel family. This channel subunit has significant amino acid identity (25-40%) with members of GABAA and GABAC receptor subunits and thus may represent a new subfamily of the GABA receptor channel. Although we cannot rule out that this clone encodes a receptor for an unidentified ligand, it was termed GABA chi. This gene is mainly expressed in placenta and in heart; however, placenta appears to express only an unspliced mRNA. In situ hybridization reveals that the GABA chi subunit mRNA is present in the electrical conduction system of the human heart. Our results suggest that novel GABA receptors expressed outside of the CNS may regulate cardiac function.

Base Sequence↗
PubMed1996

Ultrastructural localization of D1 dopamine receptor immunoreactivity in rat striatonigral neurons and its relation with dopaminergic innervation.

We have investigated by immunohistochemistry the cellular and subcellular distribution of the D1 dopamine receptor (D1R) in the rat striatonigral complex and its relation with the dopaminergic innervation. In the striatum, single pre-embedding immunoperoxidase and immunogold labeling demonstrate that D1R is mainly located on dendritic shafts and spines of spiny dendrites. D1R is also found in association with the plasma membrane of half of the perikarya of medium spiny neurons. Double labeling experiments allowing the simultaneous detection of D1R and of tyrosine hydroxylase (TH) demonstrate that D1R distribution does not match dopamine innervation: a majority of the receptors is located at sites distant from dopamine profiles and there is no significant D1R enrichment at sites of membrane appositions between dopamine and D1R profiles. In the substantia nigra, D1R is located at pre-synaptic sites on small diameter axons which are not in contact with TH-positive elements, and on terminal boutons forming symmetrical synapses on TH-positive or negative dendrites. These data demonstrate abundance and wide distribution of D1R at various extrasynaptic sites in the striatum and the substantia nigra, bringing strong evidence of anatomical basis for dopamine non-synaptic volume transmission in the rat striatonigral complex.

Animals↗
PubMed1996

Ontogeny of the striatal neurons expressing the D1 dopamine receptor in humans.

We studied D1 dopamine receptor (D1R) gene expression in the human striatum during ontogeny by in situ hybridization, immunohistochemistry, and D1R ligand autoradiography. D1R mRNA, protein, and binding sites ([3H]SCH 23390) were detected in the striatum from week 12 of fetal life. At this time, D1R mRNA was predominant in the striosomal neurons; D1R immunoreactivity (D1R-IR) and D1R binding sites displayed a pattern similar to D1R mRNA. D1R-IR was essentially present in striosomal cell bodies and neuropil, whereas only a few cell bodies were detected in the matrix. From week 20 of fetal life, D1R gene expression developed in the matrix neurons as well, thus leading to an even D1R mRNA expression throughout striosomes and matrix compartments at birth. Comparative analysis of the expression of D1R and dynorphin mRNA show the same developmental patchy pattern up to week 26. Indeed, neurons expressing the D1R gene contain dynorphin mRNA; in contrast, they do not express the preproenkephalin A gene. At birth, the pattern of D1R mRNA expression level was sharply different from that of dynorphin (DYN) gene expression. High DYN mRNA expression was restricted to the striosomes, whereas high D1R mRNA expression was present in the whole striatum. These results demonstrate that, during human ontogeny, functional D1 receptors are expressed as early as week 12 in the striatum, developing initially in the striosomal neurons containing high dynorphin mRNA content. Toward the end of fetal life, there is a dissociation between D1R and DYN expression levels, suggesting that neuroanatomical or neurochemical modifications occur at this period, which may contribute to the regulation of the tone of the striatal D1R and DYN gene with topological specificity.

Corpus Striatum↗
PubMed1996

Expression of glutamate receptors in the human and rat basal ganglia: effect of the dopaminergic denervation on AMPA receptor gene expression in the striatopallidal complex in Parkinson's disease and rat with 6-OHDA lesion.

The overactivity of subthalamopallidal and corticostriatal glutamatergic neurons observed in Parkinson's disease (PD) suggests that antagonists of glutamate receptor could be used to alleviate the motor symptoms of the disease. In this study, we analysed two features of the striatopallidal complex: (1) the distribution of alpha-amino-3 hydroxy-5-methyl-4-isoxasol-propionate (AMPA) and kainate receptors and their corresponding mRNA by immunohistochemistry and in situ hybridisation and (2) the effect of dopaminergic denervation on AMPA receptor gene expression in PD patients and rats with 6-hydroxydopamine (6-OHDA)-induced degeneration of the nigrostriatal dopaminergic system. All AMPA receptor mRNAs and proteins (GluR1-4) were detected in the internal segment of the globus pallidus (GPi). Among kainate receptors, only KA1 and KA2 were detectable and only at a low level. Only GluR4 protein was detected in the neuropil of the GPi. In the striatum, GluR1, GluR2, and GluR3 were detected in about 70% of medium-sized and large neurons. By contrast, GluR4 mRNA was detected in only a small number of large and medium-sized neurons. Among kainate receptors, GluR6, GluR7, and KA2 were detected in about 50-60% of medium-sized neurons, whereas GluR5 and KA1 were restricted to 1-2% and 20-30% of these neurons, respectively. These results suggest that antagonists of AMPA and kainate receptors could be effective in alleviating motor symptoms in Parkinson's disease by blocking the overstimulation of pallidal and striatal neurons by glutamate. A significant decrease in GluR1 gene expression (-33%) was observed in the neurons of the GPi in PD patients and in rat entopeduncular nucleus ipsilateral to the 6-OHDA lesion (-20%). GluR2, GluR3, and GluR4 mRNA levels in the GPi and GluR1-4 levels in the striatum were unchanged in PD patients and 6-OHDA-lesioned rats compared with their respective controls. These data suggest that dopamine positively regulates only GluR1 gene expression in the GPi.

Animals↗
PubMed1996

Glial cell line-derived neurotrophic factor (GDNF) gene expression in the human brain: a post mortem in situ hybridization study with special reference to Parkinson's disease.

Glial cell line-derived neurotrophic factor (GDNF) is a potent neurotrophic factor for dopaminergic neurons. Since dopaminergic neurons degenerate in Parkinson's disease, this factor is a potential therapeutical tool that may save dopaminergic neurons during the pathological process. Moreover, a reduced GDNF expression may be involved in the pathophysiology of the disease. In this study, we tested whether altered GDNF production may participate in the mechanism of cell death in this disease. GDNF gene expression was analyzed by in situ hybridization using riboprobes corresponding to a sequence of the exon 2 human GDNF gene. Experiments were performed on tissue sections of the mesencephalon and the striatum from 8 patients with Parkinson's disease and 6 control subjects matched for age at death and for post mortem delay. No labelling was observed in either group of patients. This absence of detectable expression could not be attributed to methodological problems as a positive staining was observed using the same probes for sections of astroglioma biopsies from human adults and for sections of a newborn infant brain obtained at post-mortem. These data suggest that GDNF is probably expressed at a very low level in the adult human brain and its involvement in the pathophysiology of Parkinson's disease remains to be demonstrated. GDNF may represent a powerful new therapeutic agent for Parkinson's disease, however.

Aged↗
PubMed1996

Acetic acid visualization of the cervix: an alternative to cytologic screening.

OBJECTIVE: To investigate the value of acetic acid visualization of the cervix as an alternative to cytologic screening. METHODS: A prospective study was conducted in a squatter area in Cape Town, South Africa, on 2426 women who underwent speculum examination, naked-eye inspection of the cervix after application of acetic acid, and cytologic smear. The smears were stained and processed at the screening site. Patients with a positive reading after acetic acid or a smear indicating a high-grade squamous intraepithelial lesion (SIL) were referred for immediate colposcopy, biopsy, and when indicated, treatment by large loop excision of the transformation zone. Therefore, histology was obtained on all patients with a positive acetic acid test or a positive cytology. RESULTS: Seventy-six women with positive reactions to acetic acid. Among the 2350 women with negative reactions, 254 had positive cervical smears; only 11 of these had histologic high-grade SIL. In contrast, 20 of the 61 women with positive cytology and positive acetic acid test had high-grade SIL on histology. Therefore, the acetic acid reaction enabled the observer to detect 20 of the 31 women (64%) who exhibited a high-grade SIL both on cytology and histology. CONCLUSION: In locations where access to cytopathology is limited, naked-eye visualization of the cervix after application of diluted acetic acid warrants consideration as an alternative in the detection of cervical premalignant lesions.

Acetates↗
PubMed1996

Expression of the D3 dopamine receptor in peptidergic neurons of the nucleus accumbens: comparison with the D1 and D2 dopamine receptors.

The D3 dopamine receptor, belonging to the D2-like receptor subfamily, displays both specific pharmacology and a unique pattern of expression, especially compared to the D1 and D2 receptors. A rat D3 complementary RNA probe labelled with [35S]UTP was used to map the neurons expressing the D3 receptor gene in the rat brain. In particular, we identified the phenotype of the neurons containing D3 messenger. RNA in the nucleus accumbens, with respect to the striatal segregated populations of enkephalin and substance P neurons, by using strategies of double in situ hybridization. In addition, comparison with D1 and D2 receptor gene expression was performed to study the potential co-localization of several dopamine receptors within the same neurons in the ventral striatum. The highest level of D3 messenger RNA was detected in the islands of Calleja and the nucleus accumbens. Other areas such as the caudate-putamen, some hypothalamic, thalamic and cortical areas and lobule 10 of the cerebellum also contained low but significant levels of D3 messenger RNA. Our results demonstrate that the D3 receptor is co-expressed either with D1 or with D2 receptor, both in the core and shell regions, in a subpopulation of substance P and enkephalin neurons, respectively. They also suggest that a significant part of the accumbal neurons only express either D1 or D2, without co-expression with the D3 receptor. These data imply that dopamine in the nucleus accumbens may act on each population of efferent neurons via the co-expression of two distinct dopamine receptors (D1+D3 or D2+D3), and that synergistic D1-like/D2-like effects may occur at the level of a single neuron, through the co-expression of D1 and D3 receptors in a significant proportion of substance P neurons (16% or 26% in the core and shell regions, respectively.

Animals↗
PubMed1996

Can cervical cancer be prevented by a see, screen, and treat program? A pilot study.

OBJECTIVE: Our purpose was to determine the feasibility of providing a cervical screening facility to the underprivileged communities through an educational program and a mobile clinic in which cytologic smears could be taken, screened immediately, and, when appropriate, the patients treated on site with minimal delay. STUDY DESIGN: A prospective study was conducted in two parts on 5045 patients living in squatter areas around Cape Town, South Africa. The patients were educated about cervical cancer and its prevention and were offered a free Papanicolaou smear taken in a fully equipped mobile clinic. These were immediately stained and processed. Patients diagnosed cytologically as having high-grade squamous intraepithelial lesions were assessed colposcopically and, when indicated, immediately treated by large loop excision of the transformation zone under local anesthesia. RESULTS: In phase 1, colposcopy was done in the nearest colposcopy clinic, 20 km from the screening site. The defaulter rate was 66%. In phase 2, colposcopy and treatment were offered on site. A total of 97% of patients referred for colposcopy attended the clinic, and all patients requiring treatment have been adequately treated. CONCLUSION: With a rapid turnaround time for the reporting of cytologic results and given a colposcopy and treatment facility available located at the screening site at the time women receive their results, the majority of women will undergo colposcopy and treatment.

Adult↗
PubMed1996

CD30-positive cutaneous large cell lymphomas. A comparative study of clinicopathologic and molecular features of 16 cases.

The authors have analyzed and compared the clinicopathologic and molecular features of 16 cases of large cell cutaneous lymphomas expressing CD30 antigen. Three main clinical groups were defined: (1) a group of localized skin disease (7 cases); (2) a group of multicentric skin disease (5 cases); and (3) a group of concomitant skin and extracutaneous disease. Good prognosis was associated with localized skin disease and no history of lymphoma. Interestingly, a majority of Reed Sternberg-like cells was only observed in this group (5 of 6 cases). The two other groups did not show distinctive evolutive nor morphologic features. Southern blot and/or polymerase chain reaction (PCR) technique showed clonality and a T-cell genotype in respectively 13 of 14 and 12 of 12 analyzed cases. Viral infection of tumoral cells was investigated by PCR, in situ hybridization (ISH) or electron microscopy. Epstein-Barr virus (EBV) sequences were detected by PCR and ISH in tumoral cells of cutaneous lesions in one case of skin lymphoma with extracutaneous spreading. No EBV sequence was detected by ISH in the localized lymphomas, whereas HIV particles were visible in tumoral cells in one of these cases. No human T-cell lymphotropic virus (HTLV) tax sequence was amplified by PCR in any case of our series. Our results confirm that CD30-positive cutaneous large cell lymphomas are different clinical and molecular entities. However, a combined clinical and morphologic analysis may help to identify a subset of CD30 cutaneous lymphomas with favorable prognosis.

Adolescent↗
PubMed1996

Phenotype of striatal cells expressing c-Fos following amphetamine treatment of rats with intrastriatal dopaminergic grafts.

Activation of the nigrostriatal dopaminergic system by psychostimulants such as amphetamine increases c-Fos expression in the striatum, mostly in the striatonigral substance P-ergic pathway. This effect is greatly reduced in the neostriatum deprived of dopaminergic afferents. Dopaminergic grafts implanted into the denervated neostriatum restore the reactivity of the striatum to amphetamine. However, the number of striatal neurons expressing c-Fos is greatly increased in the graft-bearing striatum compared with the normal striatum. We examined whether this increase in the number of c-Fos-expressing neurons corresponds to the recruitment of a new neuron population, or whether it reflects an increase in the proportion of substance P-ergic neurons exhibiting activation of c-Fos. Adult rats received a unilateral 6-hydroxydopamine lesion of the ascending dopaminergic mesotelencephalic pathway, and a suspension of embryonic mesencephalic neurons was subsequently implanted into the denervated neostriatum. Three months after implantation, animals were injected with d-amphetamine (5 mg/kg) and killed 2 h later. In the first experiment, striatal sections were processed to visualize both c-Fos protein, by immunohistochemistry, and preproenkephalin A or substance P, by in situ hybridization. In the second experiment, c-Fos and neuropeptide Y were visualized on the same sections. In addition, some sections incubated with anti-c-Fos antibody were counterstained with toluidine blue in order to determine whether cholinergic neurons were expressing c-Fos following amphetamine treatment. The density of neurons expressing c-Fos following amphetamine treatment was three-fold higher in the graft-bearing striata than in the striata of control animals. Approximately 75% of the c-Fos expressing cells were substance P-ergic in control animals whereas 6% were enkephalinergic and only a few were neuropeptide Y-ergic or cholinergic. Similar proportions were found in the graft-bearing striatum, signifying that the pattern of activation of c-fos following amphetamine administration is not changed by the graft. Thus, the increased expression of c-Fos predominantly reflects a graft-induced increase in the proportion of neurons expressing c-Fos within the same population of neurons which normally expresses c-Fos in the striatum, i.e. the striatonigral substance P-ergic neurons; there is no recruitment of a new neuronal population. This increased activation of the striatonigral substance P-ergic pathway may underlie the abnormal behavioural reactions brought about by amphetamine-induced stimulation of the implanted dopaminergic neurons.

Amphetamine↗