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J N Joyce

Publications and source records attributed to J N Joyce.

At least 55 records · Page 3Linked to original sources
PubMed1993

D1 and D2 dopamine receptors do not up-regulate in response to neonatal intrastriatal 6-hydroxydopamine lesions.

The extent of dopamine (DA) depletion appears to exert important influences on the plasticity of the DA system following lesions made in adulthood. The aim of this study was to determine if the extent of DA depletion has long-term effects on DA receptor regulation after early neonatal lesions. Early intrastriatal injections of 6-hydroxydopamine (6-OHDA) caused a dose-dependent loss of high-affinity DA uptake sites and mu-opioid receptor patches evident in adulthood. DA receptors did not up-regulate in response to any degree of neonatal DA depletion. A patchy loss of D1 binding was evident following the neonatal lesions, although the loss was somewhat more severe and uniform with the highest dose of 6-OHDA (20 micrograms per striatum). There was also a slight decrease in D2 binding which was not dose-dependent. These results suggest that the consequences of early neonatal DA lesions are not dependent upon the degree of DA depletion, as the effects on DA receptor expression were similar regardless of the extent of the lesions.

Animals↗
PubMed1993

Dopamine D2 receptors in the hippocampus and amygdala in Alzheimer's disease.

Receptor autoradiography was used to quantify the number of dopamine D2 receptors labeled with [125I]epidepride in the medial temporal lobe of seven cases of Alzheimer's disease in comparison to eight cases of neurologically intact controls. The Alzheimer's disease cases showed the greatest losses of D2 receptors in the basolateral nucleus of the amygdala and molecular layer of the dentate gyrus and the smallest differences from controls in the perirhinal region and subiculum. The loss of D2 receptors in the hippocampus and amygdala of cases with Alzheimer's disease in concert with alterations in dopaminergic innervation could contribute to the clinical symptoms of this disorder.

Alzheimer Disease↗
PubMed1993

Differential response of striatal dopamine and muscarinic cholinergic receptor subtypes to the loss of dopamine. III. Results in Parkinson's disease cases.

The distribution and number of DA uptake sites, DA receptors (D1 and D2) and cholinergic muscarinic receptors (M1 and M2) were examined by autoradiography in the striatal complex of Parkinson's and age-matched control cases. The greatest loss of DA uptake sites occurred in the dorsolateral striatum which was the only region showing an increase in D2 receptors. The number of M2 receptors was reduced in the dorsolateral striatum and M1 receptors were reduced in most regions of the striatum. The anatomical pattern of changes in DA uptake sites, D2 receptors and M2 receptors suggests a coordinated change in the dopaminergic-cholinergic interneuron synapse in Parkinson's disease.

Aged↗
PubMed1993

The dopamine hypothesis of schizophrenia: limbic interactions with serotonin and norepinephrine.

The "dopamine hypothesis" of schizophrenia has been the predominant guiding theoretical construct for driving studies of the neurobiology of schizophrenia. There has, however, been much interest in the contributions of non-dopamine systems to the clinical symptoms of schizophrenia, in particular, norepinephrine and serotonin. However, direct evidence for altered transmission in monoamine systems has been quite limited. In part this reflects a focus on specific brain regions for different transmitters, in contrast to a "neural systems" approach. Thus, evidence for the dopamine hypothesis has been derived from studies of the basal ganglia in schizophrenic cases and infrequently from other (e.g. cortical) regions. Recent studies have suggested that disturbances in the organization or development of the temporal lobe may underlie certain aspects of the symptoms of schizophrenia In particular, the hippocampus may show cellular loss or disturbances in cell orientation. These results are supported by the work that has identified neuropsychological and in vivo brain disturbances in schizophrenia specific to the medial temporal lobe. However, not all cases show such pathology and it is likely that these disorders could, in addition, involve an important afferent and/or efferent system associated with the temporal lobe. This model is based on the currently held view that parallel cortico-striatal-pallidal-thalamo circuits form an important basis for information processing in the brain. One such circuit involves the primary efferent of the hippocampus, the subiculum, and associated cortical regions that project onto the ventral striatum. Many of the cortical regions that project directly to the ventral striatum also project to the hippocampus via the entorhinal cortex. These include the anterior cingulate, posterior cingulate, superior temporal cortex, and inferior temporal cortex. The ventral striatum, made up of the nucleus accumbens, olfactory tubercle, and ventral putamen, has as its target the ventral pallidum. The ventral pallidum projects to the medial dorsal nuclei of the thalamus, which, in turn, projects to the anterior prefrontal cortical area. This loop has been referred to as the limbic loop. The patterns of innervation and expression of monoamine receptors in the brain have been delineated for the non-human primate and are being unraveled in the human. We, and other, have described the patterns of receptor expression in the limbic circuit. However, few studies have been published to date that detail what the neurochemical counterparts of the neuronal and neuropsychological disturbances in the limbic circuit might be. We have explored the possibility that monoamine systems are altered at more than one synaptic station in this circuit.(ABSTRACT TRUNCATED AT 400 WORDS)

Dopamine↗
PubMed1993

Substance P receptors are differentially affected in Parkinson's and Alzheimer's disease.

We have quantified by receptor autoradiography the number of NK1 receptors, using [125I] Bolton-Hunter labeled substance P, in striatum and pallidum (internal (GPi) or external (GPe) segment) of patients suffering from Alzheimer's (AD) and Parkinson's disease (PD). When compared to non-neurologic controls, a significant increase in the number of NK1 sites has been observed in the striatum of PD patients. No significant differences were observed for the GPi and GPe. We observed no significant differences from controls in the number of NK1 sites in the striatum and pallidum of AD cases. However, the number of NK1 sites in the striatum of AD patients was significantly lower than that of PD patients. These results show that the expression of NK1 receptors in the basal ganglia is affected in PD.

Aged↗
PubMed1993

Serotonin uptake sites and serotonin receptors are altered in the limbic system of schizophrenics.

Serotonin (5-HT) uptake sites were mapped by autoradiographic means with [3H]cyano-imipramine ([3H]CN-IMI), the 5-HT1A receptor with [3H]8-hydroxy-2-[di-n-propyl-amino]tetralin ([3H]8-OH-DPAT), and the 5-HT2 receptor with both [3H]ketanserin and [125I]lysergic acid diethylamide ([125I]LSD) in eight nonneurologic controls and 10 cases with a diagnosis of schizophrenia. In the striatum, there was a marked heterogeneous patterning of 5-HT uptake sites that corresponded to the striosomal/matrix compartmentalization of the striatum. This organization was not matched with an equally heterogeneous pattern of either 5-HT2 or 5-HT1A receptors. For the isocortex, a general organizational scheme was observed with the 5-HT1A receptor expression high in the external laminae and deep laminae, but 5-HT2 receptor expression was higher in the internal laminae. There was a laminar distribution of 5-HT uptake sites that approximated the combined distributions of the 5-HT1A receptor and the 5-HT2 receptor. In the parahippocampal gyrus and hippocampus, the distribution of 5-HT uptake sites was complementary to the distribution of 5-HT1A and 5-HT2 receptors. In schizophrenic cases, there was a large increase in the number and altered striosomal/matrix organization of 5-HT uptake sites in the striatum. There was also an increase in the numbers of 5-HT2 receptors in the nucleus accumbens and ventral putamen of the schizophrenics. The number of 5-HT1A receptors was not modified. There was a marked reduction in 5-HT uptake sites in the external and middle laminae of the anterior cingulate, frontal cortex, and posterior cingulate, and no changes were observed in the motor cortex, temporal cortex, or hippocampus. Increased numbers of 5-HT1A receptors were found in the posterior cingulate, motor cortex, and hippocampus. Serotonin2 receptors were substantially elevated in the posterior cingulate, temporal cortex, and hippocampus, but not in the frontal, anterior cingulate, or motor cortices. Examination of the temporal lobe and hippocampus of a group of nonschizophrenic suicides (n = 8) indicated the alterations in 5-HT system in the limbic regions of the striatum, the limbic cortex, and hippocampus of the schizophrenic cases may be disease specific.

Adolescent↗
PubMed1993

Neonatal 6-OHDA lesions upregulate adult expression of tyrosine hydroxylase mRNA.

We explored the consequences of postnatal day 1 (P1) intrastriatal 6-hydroxydopamine (6-OHDA) lesions on the developing mesostriatal dopamine system by performing in situ hybridization histochemistry for tyrosine hydroxylase (TH) in the substantia nigra-ventral tegmental area (SN-VTA) complex of neonatally-lesioned and non-lesioned animals at P90. There were significant reductions in the expression of TH mRNA from both the rostral and caudal levels of the lateral and medial SNc of 6-OHDA treated animals. The VTA was preferentially spared from the neurotoxic effects of 6-OHDA and showed elevated levels of TH mRNA in the caudal VTA compared with controls. This heterogeneous pattern of TH mRNA expression suggests that early intrastriatal 6-OHDA lesions selectively damage certain DA systems and affect the development of other systems.

Animals↗
PubMed1993

Serotonergic involvement in haloperidol-induced catalepsy.

The ability of serotonin (5-HT)-selective compounds to reverse catalepsy due to blockade of dopamine (DA) receptors was examined in rats treated with the antipsychotic haloperidol (HAL). The 5-HT-releasing drug fenfluramine significantly reversed HAL-induced catalepsy. The 5-HT1A receptor agonists 8-hydroxy-2-(di-n-propylamino)tetralin and buspirone potently and dose-dependently reversed HAL-induced catalepsy. The effect of 8-hydroxy-2-(di-n-propylamino)tetralin was blocked by pretreatment with the 5-HT1A/1B receptor antagonist pindolol, but not the 5-HT2 receptor antagonist ketanserin. The 5-HT1C/2 receptor agonist 2,5-dimethoxy-4-bromoamphetamine also completely reversed HAL-induced catalepsy, an effect blocked by ketanserin, but not pindolol. Neither antagonist alone had any effect. The 5-HT1B/1C receptor agonist trifluoromethylphenylpiperazine only partially reversed HAL-induced catalepsy, and the effect was not dose dependent. The 5-HT1C/2 receptor antagonist mianserin reversed HAL-induced catalepsy on its own; therefore, its ability to block the effect of trifluoromethylphenylpiperazine could not be tested. The nature of the disruption of HAL-induced catalepsy was examined by measuring the ability of increasing doses of HAL to surmount the effects of the serotonergic agonists. The mixed DA-D1/D2 receptor agonist apomorphine shifted the dose-effect curve for HAL to the right in a parallel manner, indicative of a competitive interaction between HAL and apomorphine at the D2 receptor. In contrast, the 5-HT receptor agonists flattened the dose-effect curve for HAL, suggestive of noncompetitive interactions. These data suggest that the 5-HT receptor agonists are not reversing HAL-induced catalepsy by indirectly increasing DA release. Rather, the agonists reverse HAL-induced catalepsy through interactions at their specific 5-HT receptor subtypes. Thus, the 5-HT receptor agonists may provide novel approaches for the development of drugs which can reverse or prevent the extrapyramidal side effects associated with antipsychotic treatment.

Animals↗
PubMed1992

Visualization of dopamine D3-like receptors in human brain with [125I]epidepride.

In sections of human brain containing the striatum (caudate, nucleus, putamen, nucleus accumbens) the competition for binding of [125I]epidepride by compounds with differing selectivity for dopamine D2 and D3 receptors was examined. Domperidone showed higher affinity for D2-like than D3-like sites whereas 7-OH-DPAT (7-hydroxy-2-(N,N-di-n-propylamino)tetralin) and quinpirole demonstrated the reverse selectivity. The pattern of [125I]epidepride binding in the presence of a high concentration of domperidone was negligible in the dorsal striatum but indicated islands of dense binding to D3-like receptors in the nucleus accumbens and ventral putamen.

Autoradiography↗
PubMed1992

Distribution of beta-adrenergic receptor subtypes in human post-mortem brain: alterations in limbic regions of schizophrenics.

The distribution of the beta 1 (beta 1) and beta 2 (beta 2) subtypes of the beta-adrenergic receptor was examined in rat and nondiseased control human tissue. The distribution of the beta 1 and beta 2 receptors was also examined in schizophrenic cases, with additional studies in schizophrenic suicide and nonschizophrenic suicide cases. Scatchard analysis of the binding of [125I]iodopindolol (IPIN) to cortical membranes showed a similar Kd in human (177 pM) and rat (161 pM), but a lower maximum binding site (Bmax) in the human tissue (18.7 fmol/mg protein and 55.6 fmol/mg protein). For the autoradiographic studies [125I]IPIN was used to visualize both subtypes (total) or was displaced with the selective beta 1-receptor antagonist ICI-89,406 to visualize beta 2 sites, or with the selective beta 2-receptor antagonist ICI-118,551 to visualize beta 1 sites. Important differences in the regional distribution of the two subtypes of the beta-adrenergic receptors were noted between rat and human. In the nucleus accumbens and ventral putamen (ventral striatum), a patchy distribution of beta 1 receptors was observed that was not evident in the rat. These patches were aligned with markers of the matrix compartment of the striatum. The schizophrenic cases showed significant increases in the labeling of the beta 1-receptor patches with [125I]IPIN. In contrast to the frontal cortex of the nondisease controls, the parietal and temporal cortex showed a high ratio of beta 1 to beta 2 receptors and a highly laminar organization of the subtypes. [125I]IPIN binding to beta 1 receptors was highest in the external laminae with the reverse gradient for the beta 2 subtype. The medial temporal cortex displayed an alteration in the ratio of the 2 subtypes of the beta-adrenergic receptor, with the parahippocampus and hippocampus of the human, in contrast to the rat brain, predominantly expressing the beta 2 receptor. Moreover, there were consistently higher densities of beta 2 receptors in the hippocampus of the right hemisphere than the left hemisphere of the nondisease controls. There was not a left and right hemispheric asymmetry of beta 2 receptors in the hippocampus of elderly schizophrenics or in young schizophrenics who committed suicide. The asymmetry was evident in nonschizophrenic suicides, suggesting that the lack of asymmetry in the hippocampus of schizophrenics is evident early in the disease process. Thus limbic structures show alterations in the patterning of beta 1 and beta 2 receptors in the schizophrenic cases.

Adult↗
PubMed1992

Neonatal 6-OHDA lesions differentially affect striatal D1 and D2 receptors.

Lesions to the dopamine (DA) system in early postnatal development have different behavioral consequences compared to lesions made in adulthood. Intrastriatal injections of the neurotoxin 6-hydroxydopamine (6-OHDA) on the day of birth (PO) or postnatal day 1 (P1) produce a selective supersensitivity to D1 receptor agonists and a subsensitivity to D1 antagonists (Neal and Joyce, 1991a). In this paper, we describe the long-term effects of early DA loss on DA receptor regulation. Pups received bilateral intrastriatal injections of the neurotoxin 6-OHDA (4 micrograms per striatum) on PO or P1. Adult rats were killed at 90 days of age and the brains were processed for quantitative autoradiography (QAR) or tyrosine hydroxylase (TH) immunocytochemistry. Cohorts were tested for the behavioral responses to the selective D1 receptor agonist SKF38393 (10 mg/kg). Neonatally lesioned rats exhibited increases in abnormal perioral movements in response to D1 receptor stimulation. There was a heterogenous and patchy loss (40-50%) of [3H]mazindol binding to high-affinity DA uptake sites (a marker of DA terminal density) and a similar loss of TH-like immunoreactivity within the striata of the neonatally lesioned rats. There was also a reduction in the number of mu-opioid receptor patches (labelled with [3H]naloxone), a marker for the striatal patch compartment, and a similar patchy loss of D1 binding sites (labeled with [3H]SCH23390). The binding of [3H]spiroperidol to D2 sites was not altered. This is in contrast to the changes observed following adult 6-OHDA lesions, wherein there is a significant increase in the number of D2 binding sites (Joyce, 1991a,b). The results are discussed with respect to the behavioral consequences of neonatal lesions and the differences between neonatal and adult lesions.

Animals↗
PubMed1991

Dopamine D1 receptor behavioral responsitivity following selective lesions of the striatal patch compartment during development.

The behavioral effects of selective destruction of the dopamine (DA) input to the patch compartment of rat striatum early in development was investigated. Rat pups were given bilateral intrastriatal (i.s.) injections of the neurotoxin 6-hydroxydopamine (6-OHDA) on day of birth (P0) or postnatal day 1 (P1), which resulted in selective behavioral alterations following DA agonist treatment in adulthood. Neonatally-lesioned rats exhibited self-biting behavior following treatment with the DA precursor L-dihydroxyphenylalanine (L-DOPA). In response to treatment with the selective D1 agonist SKF38393, there was an increased incidence of abnormal perioral movements. The cataleptogenic effects of the D1 antagonist SCH23390 and the D2 antagonist haloperidol were also studied. Neonatally-lesioned rats were significantly less cataleptic compared to control rats following D1 antagonist treatment, but not following D2 antagonist treatment. Autoradiographs of [3H]mazindol binding to DA uptake sites (a measure of DA terminal density) showed a 'patchy' loss of approx. 40-50% in striatal tissue sections derived from the i.s. lesioned rats. These data suggest that injections of 6-OHDA into the striatum during this early postnatal period cause a DA lesion that results in long-term effects on a D1 receptor system.

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗
PubMed1991

Ontogeny of dopamine D1 and D2 receptor subtypes in rat basal ganglia: a quantitative autoradiographic study.

The ontogeny of D1 and D2 dopamine (DA) receptors in rat basal ganglia was examined by quantitative autoradiography using the iodinated ligands [125I]SCH 23982 and [125I]iodobenzamide [( 125I]IBZM), respectively. Temporal and spatial differences in the development of the receptor subtypes were observed. Scatchard transformation of saturation isotherms conducted at postnatal day 10 (P10) and P60, showed that there was no age-related change in the affinity of [125I]SCH 23982 binding to D1 receptors (Kd = 2.6 nM) but there was a significant increase in the Bmax (771 compared to 2032 fmol/mg protein, P = 0.002). A statistically significant difference in Kd was noted between ages P10 and P60 for [125I]IBZM labelling of D2 receptors (0.62 vs 1.00 nM, respectively, P less than 0.01). A significant increase in the Bmax (211 and 721 fmol/mg protein, P less than 0.01) was also observed. D1 receptors were visible as distinct patches at P1. The highest density was found in the ventrolateral caudate-putamen (CPu). By P5 the patches were found in all subregions of the CPu and nucleus accumbens. Between P7 and P10 the binding became distinctly less patchy due to a marked increase in the density of D1 receptors in non-patch (matrix) regions. Adult levels of receptor were seen by P30. The concentration of DA (measured by HPLC) and binding of [3H]mazindol to DA uptake sites in whole striatum showed similar and nonlinear increases with age. The age-related change in the topography of binding sites for [3H]mazindol was similar to that of D1 receptors at the same ages. Both D2 receptors and [3H]hemicholinium-3 (HC-3) binding to high affinity transport sites for choline developed initially in the dorso-lateral CPu. Their topography was largely overlapping but distinct from that of the D1 receptor. D2 receptors were not consistently observed until P3 in the CPu, and zones of enriched binding were aligned with zones of low density for D1 receptors. The density of D2 receptors reached adult levels by P30. The differential development of the DA receptors was also evident in the substantia nigra (SN) and globus pallidus (GP). D1 receptors were found in SN prior to the appearance of D2 receptors and throughout development the density was greater in pars reticulata than in pars compacta, whereas the density of D2 receptors was higher in the pars compacta. At all ages the density of D1 receptors was greater than the density of D2 receptors in the GP and reached adult levels before reaching it in the CPu or SN.(ABSTRACT TRUNCATED AT 400 WORDS)

Aging↗
PubMed1991

Differential response of striatal dopamine and muscarinic cholinergic receptor subtypes to the loss of dopamine. I. Effects of intranigral or intracerebroventricular 6-hydroxydopamine lesions of the mesostriatal dopamine system.

Quantitative autoradiography was utilized to examine the response of the dopamine (DA) and muscarinic cholinergic system within the striatum to lesions of the mesostriatal DA system following intranigral 6-hydroxydopamine (6-OHDA) injections. In addition, the response of DA system was examined in the striatum of animals treated with low, medium, or high doses of 6-OHDA made intracerebroventricularly (icv). Three weeks following removal of the mesostriatal DA fibers with intranigral 6-OHDA, there was an almost complete depletion of DA and [3H]mazindol binding throughout the striatum. The resulting increase in D2 receptors labeled with [3H]spiroperidol (27%) was most evident in the lateral striatum and topographically correlated with an increase in choline uptake sites labeled with [3H]hemicholinium-3 (20%). There was a smaller but significant decrease in D1 receptors labeled with [3H]SCH 23390 (15-18%) that was not topographically related to changes in [3H]spiroperidol or [3H]hemicholinium-3 binding. All doses of icv 6-OHDA produced a significant loss of DA and of [3H]mazindol binding as compared to vehicle injections that was more pronounced in the medial than in the lateral striatum. No increase in D1 receptors was observed with any dose of 6-OHDA and greater than 90% loss of DA and [3H]mazindol resulted in an increase in D2 receptors in the lateral striatum and a reduction in D1 receptors in the dorsal striatum. These data are consistent with the evidence that there is independent regulation of the two subtypes of the DA receptor. Moreover, the distribution and regulation of the subtypes of the muscarinic receptor were independent. Muscarinic M2 receptors ([3H]N-methylscopolamine in presence of excess pirenzepine) showed a lateral to medial gradient (highest laterally) that was related to the pattern of choline uptake sites and D2 receptors. Loss of DA resulted in a reduction in M2 receptors (24-30%) that was correlated with the increase in choline uptake sites. In contrast, M1 ([3H]pirenzepine) receptors showed a reverse gradient from the M2 receptor and a smaller reduction following loss of DA.

Animals↗
PubMed1991

Differential response of striatal dopamine and muscarinic cholinergic receptor subtypes to the loss of dopamine. II. Effects of 6-hydroxydopamine or colchicine microinjections into the VTA or reserpine treatment.

In the previous paper it was demonstrated that striatal dopamine (DA) D1 and D2 receptor subtypes and muscarinic M1 and M2 receptor subtypes show differing responses to lesions of the mesostriatal DA system. To examine this differential regulation further rats were given unilateral injections of 6-hydroxydopamine (6-OHDA) or colchicine into the ventral tegmental area (VTA), or treated chronically with reserpine or saline. Two weeks later the animals were tested for their behavioral response to a subthreshold dose of apomorphine and 24 h later their brains were removed and processed for quantitative autoradiography or for analysis of DA levels by high-performance liquid chromatography. The 6-OHDA-lesioned animals showed a supersensitive rotational response to apomorphine. The loss of DA, loss of DA uptake sites, regulation of DA D1 and D2 receptors and regulation of the muscarinic cholinergic system was similar to the previous paper. Injection of colchicine in the VTA resulted in incomplete loss of striatal DA (50%), [3H]mazindol binding (50%), and no behavioral supersensitivity to apomorphine. There was a small loss of presynaptically located D2 receptors (13%). Similar to the 6-OHDA lesions there was a loss of D1 (12%) and M1 receptors. Reserpine treatment produced an 86% decrease in DA levels, an enhanced stereotyped responsiveness to apomorphine, and an increase of both D2 (28%) and D1 receptors (26%). There was a loss of muscarinic M1 but not M2 receptors. Thus removal of DA terminals or blockade of transport of proteins in the mesostriatal axons can lead to a reduction in D1 receptor density in the striatum. In contrast, loss of DA without removal of DA terminals leads to a significant up-regulation of the D1 receptor. D2 receptors show increases following removal of DA or of DA terminals. Alteration in the muscarinic cholinergic system following damage to the mesostriatal DA system is a complex response not mimicked by either reserpine or colchicine treatment.

Animals↗
PubMed1991

Characterization and distribution of [125I]epidepride binding to dopamine D2 receptors in basal ganglia and cortex of human brain.

The distribution and pharmacology of the binding of [125I]epidepride, a substituted benzamide with high affinity and selectivity for dopamine (DA) D2 receptors in rat brain (Neve et al., J. Pharmacol. Exp. Ther. 252: 1108-1116, 1990), is described in human brain. Saturation analysis of the binding of [125I]epidepride to membranes derived from striatum and regions of cortex demonstrated similar Kd values (34 and 28-33 pM, respectively) but differing maximum density of binding site values (152 and 3-8 fmol/mg of protein, respectively). The pharmacological profile of binding in cortex was also similar to striatum (epidepride greater than spiperone greater than butaclamol = flupenthixol greater than clozapine) except that an additional low-affinity site, blocked by the alpha-2 adrenergic antagonist idazoxan, was present in cortex. Quantification by autoradiography also demonstrated the greatest binding in the basal ganglia, with the striatum exhibiting greater binding than the pallidal complex or midbrain regions. For the pallidum, binding in the external segment was higher than the internal segment. Within the midbrain the binding of [125I]epidepride correlated well with the known distribution of DA-containing cell bodies, with the substantia nigra (pars compacta and pars lateralis) and ventral tegmental area (A10) higher than area A8 and central gray. Binding in frontal and parietal cortex was highest in the internal layers (layers V and VI). Temporal cortex showed a 2-fold higher density of binding than other cortical regions and a trilaminar pattern; binding was greater in the external (layers I and II) and internal layers than in the middle layers (III and IV). This pattern changed in the parahippocampal complex. Within the lateral occipitotemporal cortex, binding was densest in layers I to III and very low in layers IV to VI, but binding was almost nonexistent in the adjacent entorhinal cortex. Within the hippocampal complex, binding was evident in the subiculum, CA3 and dentate gyrus and almost nonexistent in the presubiculum or other fields of the hippocampus. This pattern of binding in the parahippocampal gyrus is unique to human brain and represents sites of action for DA in limbic cortex.

Adult↗