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J N Joyce

Publications and source records attributed to J N Joyce.

At least 73 records · Page 4Linked to original sources
PubMed1990

Striosomal organization of cholinergic and dopaminergic uptake sites and cholinergic M1 receptors in the adult human striatum: a quantitative receptor autoradiographic study.

The distribution of cholinergic pre- and postsynaptic markers and dopaminergic presynaptic markers was analyzed in the adult human striatum, using quantitative receptor autoradiography. The distribution of the different binding sites indicates that cholinergic and dopaminergic uptake sites display a striosomal organization, with a higher binding site density in the striatal matrix. M1 muscarinic cholinergic receptor distribution parallels the distribution of cholinergic presynaptic markers. Our data show that cholinergic and dopaminergic terminals, and M1 receptors are enriched in the matrix of the adult human striatum.

Aged↗
PubMed1989

Decreased striatal D1 binding density following mesotelencephalic 6-hydroxydopamine injections: an autoradiographic analysis.

Autoradiographic experiments performed on rats with unilateral mesotelencephalic 6-hydroxydopamine (6-OHDA) injections revealed reduced binding of [3H]SCH23390 to D1 receptors in the striatum ipsilateral to the neurotoxin as well as increased binding of [3H]spiroperidol to D2 receptors in that hemisphere. These opposite influences of injury on the dopamine receptor subtypes occurred in rats sacrificed at 2 weeks or 11 months postoperatively, but neither change was evident at 4 days postoperatively. Equilibrium saturation analysis performed on rats sacrificed at 8 weeks postoperatively indicated that D1 and D2 receptor changes reflected altered Bmax values without KD modifications. Topographic analysis of the D1 decline by quantitative autoradiography revealed that the D1 decrease was greater in dorsal striatum than ventrally. Those striatal regions that showed greater declines in D1 density correspondingly had the greater losses of [3H]mazindol binding after the denervation, suggesting that the decline of D1 binding is a postsynaptic consequence of the reduced mesostriatal dopaminergic innervation. The findings indicate opposite influences of injury on D2 and D1 receptor levels and raise important questions concerning the mechanism by which 6-OHDA injection affects the D1 sites.

Animals↗
PubMed1989

Regulation of muscarinic receptors in hippocampus following cholinergic denervation and reinnervation by septal and striatal transplants.

The regulation of hippocampal muscarinic M1 and M2 receptors was studied by autoradiographic methods following cholinergic denervation and reinnervation from embryonic septal transplant. In young adult male rats the density of M1 sites, labeled either with 3H-pirenzepine (PZ) or 3H-N-methylscopolamine (NMS, in the presence of excess carbachol), exceeded by 4- to 5-fold the density of M2 sites, labeled with 3H-NMS in the presence of excess PZ. Both receptors appeared to be densest in hippocampal regions lowest in acetylcholinesterase or 3H-hemicholinium-3 binding. The distribution of M1 receptors did differ from the distribution of M2 receptors within subregions of the hippocampus. Along the mediolateral axis from the subiculum to the lateral CA 1, the density of M1 receptors is uniform, but the density of M2 receptors decreases. Also apparent is the relatively small difference in density between the CA1 and dentate gyrus for M1 receptors but a significantly greater difference for M2 receptors. However, the response of M1 and M2 receptors to long-term cholinergic denervation following fimbriafornix transection of the septal cholinergic input and to cholinergic innervation by embryonic septal transplants was similar. Long-term denervation (40-60 d) resulted in a 30-60% increase in both M1 and M2 receptors within regions of the hippocampal formation. Receptor levels were reduced to normal in regions innervated by septal transplants. For both receptors, the changes in the density of sites were due to alterations in the Bmax and not the Kd for the radioligands. The specificity of this regulation is supported by the evidence that (1) the degree and topography of the normalization of muscarinic receptor density was entirely dependent on the degree and pattern of cholinergic reinnervation by the fibers of the septal transplant, (2) cholinergic fiber reinnervation by embryonic striatal grafts also down-regulated the density of M1 and M2 receptors, and (3) successfully surviving transplants (e.g., cerebellar and striatal) that did not provide innervation to the hippocampus did not induce down-regulation of muscarinic receptors. Changes in the density of sites were not related to changes in the width of the hippocampus following denervation and reinnervation. The data support the view that the majority of M1 and M2 receptors are located postsynaptically on neurons within the hippocampus and not presynaptically on cholinergic fibers.

Animals↗
PubMed1988

Organization of dopamine D1 and D2 receptors in human striatum: receptor autoradiographic studies in Huntington's disease and schizophrenia.

The technique of quantitative autoradiography was used to examine the effects of Huntington's disease (HD) and schizophrenia on the organization of striatal dopamine (DA) D1 and D2 receptors. Whereas the striatum of HD cases showed a reduction in the density of D1 ([3H]SCH 23390) and D2 ([3H]spiroperidol) receptors, the patterning of D2 receptor loss did not match that of the D1 receptor loss. The HD loss of D1 D1 receptors (65%) is far greater than the loss of D2 receptors (28%). Whereas there was a dorsal-ventral gradient of effect on both receptor subtypes, the effects of HD on D2 receptors in the ventral putamen (PUT) and nucleus accumben septi (NAS) were minimal. Similarly, muscarinic M1 and M2 receptors demonstrate different patterns of alteration in HD. The M2 subtype, labeled with [3H]N-methylscopolamine (in the presence of excess pirenzepine to occlude M1 sites), was depleted far more than the M1 receptor subtype, labeled with [3H]pirenzepine. Although the effects of HD on [3H]mazindol labeling of DA terminals were more heterogeneous, there appeared to be a relative preservation of this afferent input to the striatum of the HD cases. In the schizophrenic cases, our autoradiographic studies confirm previous reports of an elevation of D2 receptor density in the striata of many schizophrenics. This increase was evident even though two of the three cases were known to have not been treated with neuroleptics, and the third case may also have been drug naive. However, the increase was far greater in the NAS (164%) and ventral PUT (173%) than more dorsally in the striatum (68%). The density of D1 receptors and DA terminals labeled with [3H]mazindol in the striatum of schizophrenics was not significantly different from that of control cases. Thus in both HD and schizophrenia, the ratio of D2/D1 receptors is altered in favor of the D2 population, particularly in the NAS.

Aged↗
PubMed1987

[3H]hemicholinium-3 binding in rabbit striatum: correspondence with patchy acetylcholinesterase staining and a method for quantifying striatal compartments.

Comparisons were made of the distribution of acetylcholinesterase (AChE) staining and [3H]hemicholinium-3 binding in adjacent tissue sections through the rabbit striatum. The distribution of these two markers matched closely in all regions examined. Circumscribed AChE-poor zones (striosomes) were visible throughout the rostral one-third of the caudate nucleus and were aligned with areas of low [3H]hemicholinium-3 binding in adjacent sections. Quantitative analysis of the [3H]hemicholinium-3 film autoradiographs revealed a 2- to 3-fold lower binding of [3H]hemicholinium-3 to sites within the striosome compartment compared with the darker background (matrix). Further analysis revealed at least 3 distinct levels of binding throughout the striatum. The results suggest a novel autoradiographic approach for identifying and quantifying striatal heterogeneities. Because [3H]hemicholinium-3 apparently labels the high-affinity choline transport complex associated with cholinergic neurons, the patchy striatal distribution of AChE/[3H]hemicholinium-3 apparently marks zones with differing densities of cholinergic neuron processes.

Acetylcholinesterase↗
PubMed1987

Quantitative autoradiography of dopamine D2 sites in rat caudate-putamen: localization to intrinsic neurons and not to neocortical afferents.

Dopamine D2 receptors, labeled with [3H]spiroperidol or [3H]sulpiride, show a lateral-to-medial gradient in the caudate-putamen, with a more than two-fold greater density laterally than medially. It has been thought that D2 receptors are located on at least two neuronal elements of the caudate-putamen, neurons intrinsic to this structure and axons whose cell bodies reside in the cortex. As a first step in establishing what neuronal elements underlie this heterogeneous organization of D2 receptors, we took advantage of quantitative autoradiography to examine the association of these receptors with those elements. The present findings show that the D2 sites are almost exclusively located on neurons whose somata reside in the caudate-putamen and are not located on terminals of corticostriatal axons. A detailed comparison of the distribution of histochemically identified acetylcholinesterase neurons with that of D2 receptors in serially adjoining sections suggests a common organizational pattern. The density of [3H]spiroperidol sites in rat caudate-putamen was determined after unilateral injection of the neurotoxin quinolinic acid into this structure or after ablation of neocortical regions. Quantification of the tissue damage was achieved by acetylcholinesterase histochemistry (following diisopropylfluorophosphate treatment), as well as by thionin and luxol fast staining of sections adjacent to those used for [3H]spiroperidol autoradiography. In identically treated animals, biochemical determination of the extent of tissue damage was made utilizing assays for high-affinity [3H]choline and [3H]glutamate uptake in the caudate-putamen. In quinolinic acid-injected rats, the density of D2 sites was decreased by 90-95% at the site of complete loss of large acetylcholinesterase-positive neurons. Other animals, given ablations of specific neocortical fields (medial prefrontal, motor, somatosensory) or of the entire parietal-frontal cortex of one hemisphere, showed no loss of caudate-putamen D2 sites unless the cortical ablation caused accompanying damage of the caudate-putamen. In the caudate-putamen of all animals there was a close correspondence between the D2 sites and the striatal neurons (and processes) that show strong acetylcholinesterase reactivity. We suggest that the caudate-putamen topography of D2 sites is based largely on the internal organization of this structure and may preferentially involve acetylcholine-containing intrinsic neurons.

Acetylcholinesterase↗
PubMed1986

Hemiparkinsonism in a monkey after unilateral internal carotid artery infusion of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) is associated with regional ipsilateral changes in striatal dopamine D-2 receptor density.

Infusion of 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) into the right internal carotid artery of a cynomologus monkey (Macaca fascicularis) induced an almost complete loss of the dopaminergic innervation of the right caudate-putamen and hemiparkinsonism. Digital subtraction autoradiography revealed that at 8 weeks postinjection, a major increase in [3H]spiroperidol binding to D-2 sites in the lateral regions of the right caudate nucleus and putamen occurred, without a significant change in the medial caudate nucleus and putamen. The 92-96% decrease in specific [3H]mazindol binding observed in the right striatum extended into the medial caudate nucleus and putamen and confirmed the extensive loss of dopamine inputs to this structure. The region of the increase in D-2 receptor density is innervated by somatosensory, motor and parietal cortex. This indicates that the increase in D-2 receptor density in this region of the striatum may play a particularly important role in the L-dihydroxyphenylanine-induced motoric recovery observed in such animals.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗
PubMed1986

Age-related regional loss of caudate-putamen dopamine receptors revealed by quantitative autoradiography.

Senescent (26-28 months) Fischer 344 rats were shown to have a lower density of D2 sites (-36%) without any change in affinity in membranes prepared from homogenized caudate-putamen (CPU), as compared to young adult (5-6 months) rats. In additional rats prepared for quantitative autoradiography of [3H]spiroperidol binding, the loss was shown to be specific for and quite extensive (50-60%) in the lateral to ventrolateral region of the CPU. The region of the CPU that shows the major age-related loss of D2 sites is critically involved in sensorimotor functions; therefore this regional loss of D2 sites may contribute importantly to the sensorimotor deficits in aged rats.

Aging↗
PubMed1986

Effects of estrogen on the basal ganglia.

Recent research suggests that estrogen regulates the activity of dopamine-containing fibers originating in the midbrain and terminating in the basal ganglia, and/or dopamine-sensitive cells in the basal ganglia. The mechanism by which estrogen acts is not clear, since cells in neither of these regions concentrate estrogens. Nevertheless, estrogens clearly affect behaviors mediated by the basal ganglia, as illustrated in human patients suffering from extrapyramidal disorders. Both biochemical and behavioral research in animals has confirmed that estrogen modulates basal ganglia function, but there has not been agreement concerning either the locus, the direction, or the mechanism of its action. These topics are the focus of this review. The effects of estrogen on behaviors mediated by DA in the basal ganglia depend on the dose of estrogen administered, the time interval between estrogen treatment and testing, the behavior measured, and the part of the basal ganglia from which the behavior is elicited. A high dose of estrogen results in an initial suppression and later enhancement of DA-related behaviors elicited from the striatum. However, no later enhancement of these behaviors occurs if a low dose of estrogen is given. Even after low doses of estrogen, the latency to behavioral suppression varies depending upon the behavior measured. These varying latencies suggest that more than one mechanism is involved in the effects of estrogen on basal ganglia output. In addition, estrogen may also act on some regions in the mesolimbic DA system. While estrogen may act indirectly via the catechol estrogens and prolactin, it has been demonstrated that estrogen can act directly on the striatum. These findings are related to the effects of estrogen on human extrapyramidal disorders.

Acetylcholine↗
PubMed1986

Human striatal dopamine receptors are organized in compartments.

Dopamine (D2) receptors visualized in postmortem human striatum by quantitative autoradiography of [3H]spiroperidol binding are organized into circumscribed zones of low receptor density separated from other such zones by regions of higher D2 density. The D2-rich zones of the caudate nucleus and putamen contain twice the binding of D2-poor zones. The Hill coefficient, obtained from saturation analysis of [3H]spiroperidol binding to thin sections of human striatum, gave a value near unity, indicating the binding was occurring to a single type of site. The patchiness of [3H]spiroperidol binding was unaltered by postincubation removal of lipid from the tissue sections, indicating that a differential absorption of tritium in white and grey matter does not account for the heterogeneous distribution. The D2-rich and D2-poor regions appear to form labyrinths oriented in the anterior-posterior axis and are typically aligned with, respectively, acetylcholinesterase-rich and -poor compartments as visualized on stained adjacent sections. Thus, the distribution of dopamine D2 receptors conforms to the "striosomal" organization of the human caudate-putamen, a finding that suggests that this receptor subtype may mediate the influence of dopamine on distinct neurochemical compartments within the structure.

Acetylcholinesterase↗
PubMed1985

Dopamine D-2 receptors in rat caudate-putamen: the lateral to medial gradient does not correspond to dopaminergic innervation.

The topography of dopamine D-2 receptors within the rat caudate-putamen (CPU) was characterized by measuring [3H]spiroperidol binding to membranes from dissected regions of the CPU and to thin sections of rat forebrain using quantitative autoradiography. Specific binding, defined using 1 microM (+)-butaclamol, was considerably higher in the lateral CPU than the medial CPU, without any obvious gradient in the dorsoventral axis. The difference in Bmax between the lateral and medial CPU was similar whether determined by digital subtraction autoradiography of coronal forebrain sections or by [3H]spiroperidol binding to membrane homogenates derived from CPU subregions. No regional differences were observed in the affinity of [3H]spiroperidol for D-2 sites. There were no lateral-to-medial differences in the dopaminergic innervation of the CPU, as determined by the measurement of the levels of dopamine, homovanillic acid and dihydroxyphenylacetic acid in subregions of the CPU using high pressure liquid chromatography. Thus, regional variations in the density of D-2 receptors within the CPU do not correspond to the degree of dopaminergic innervation. The functional importance of the organization of this dopamine receptor system is discussed in relation to the lateral-to-medial organization of the CPU.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1985

Stereotyped behavior and diabetes mellitus in rats: reduced behavioral effects of amphetamine and apomorphine and reduced in vivo brain binding of [3H]spiroperidol.

Rats made diabetic with streptozotocin showed decreased stereotyped behaviors following administration of amphetamine or apomorphine. Spontaneous activity in an open field was lower in diabetics than in controls, but a low dose of apomorphine produced equivalent fractional decreases in activity in both groups. In vivo accumulation of amphetamine and apomorphine was generally similar in both groups: Reduced tissue access did not appear to be responsible for the decreased behavioral effects of these agents. The in vivo accumulation of spiroperidol in several brain regions was generally less in diabetics than in controls. These data are discussed in terms of altered catecholamine biochemistry and behavior in diabetics.

Animals↗
PubMed1984

Behaviors induced by intrastriatal dopamine vary independently across the estrous cycle.

Unilateral intrastriatal injections of dopamine (DA; 25 micrograms/0.25 microliters) or amphetamine ( AMPHET ; 25 micrograms/0.25 microliters) induced contralateral postural deviation and contralateral rotation that varied systematically across the estrous cycle of Long-Evans hooded rats. Both the deviation and rotation elicited by either drug were suppressed during the early part of the day of proestrus (2-6 hours after lights on) and were enhanced on the day of estrus, compared to the other days of the estrous cycle. However, when the behaviors elicited by the two drugs were examined across the day of proestrus, it was found that postural deviation and rotation changed independently. Postural deviation elicited by intrastriatal DA and AMPHET was suppressed on the day of proestrus at 4 and 7 hours after lights on, but was enhanced to the level seen during estrus at 11 hours after lights on. In contrast, contralateral rotation induced by either drug was suppressed 4, 7 and 11 hours after lights on and was enhanced only by the morning of estrus. These data suggest that there are separate DA-modulated mechanisms within the striatum for postural deviation and contralateral rotation, and that these mechanisms are differentially affected across the estrous cycle.

Animals↗
PubMed1984

Estradiol application to one striatum produces postural deviation to systemic apomorphine.

In order to test whether estrogen acts directly in the dorsal striatum to affect dopamine-mediated behavior, ovariectomized female Long-Evans rats were given a unilateral striatal application of estradiol, injected systemically with apomorphine (APO), and tested for lateralization of stereotypic behaviors. In the first experiment, estradiol, cholesterol, or an empty cannula was inserted and the rat given 0.7 mg/kg APO 1-4 hours later. Rats directed their stereotypic behaviors to the side ipsilateral to the insert of estradiol with dorsal striatal inserts, but not with inserts in ventral striatum or neocortex. Neither cholesterol nor the empty cannula inserts were effective in producing lateralization of the stereotypic behaviors. In the second experiment, intrastriatal inserts of 17 alpha-estradiol were ineffective in producing a lateralization of APO-induced stereotyped behavior. In the third experiment, several doses of APO (0.07, 0.75 and 3.0 mg/kg) were tested. At the highest dose no lateralization of APO-induced stereotypic behavior was observed. These results strongly suggest that estradiol acts directly in the dorsal striatum to antagonize APO and thus produce a lateralization of stereotypic behaviors (postural deviation).

Animals↗