Bimodal distribution of dopamine receptor densities in brains of schizophrenics.

The dopamine hypothesis of schizophrenia was examined by measuring the density of dopamine receptors in the postmortem brains of 81 control subjects and 59 schizophrenics from four different countries. The densities of dopamine receptors in the tissues from the schizophrenic patients had a bimodal distribution in the caudate nucleus, putamen, and nucleus accumbens. One mode occurred 25 percent above the control density, and a second mode occurred at a density 2.3 times that of the control density for all three regions. Although almost all the patients had been medicated with neuroleptics, the two modes had the same dissociation constant for the labeled ligand used, suggesting that the neuroleptic doses were similar for the two populations of schizophrenics. The results thus provide direct evidence for two distinct categories of schizophrenia.

Increased brain dopamine and dopamine receptors in schizophrenia.

In postmortem samples of caudate nucleus and nucleus accumbens from 48 schizophrenic patients, there were significant increases in both the maximum number of binding sites (Bmax) and the apparent dissociation constant (KD) for tritiated spiperone. The increase in apparent KD probably reflects the presence of residual neuroleptic drugs, but changes in Bmax for tritiated spiperone reflect genuine changes in receptor numbers. The increases in receptors were seen only in patients in whom neuroleptic medication had been maintained until the time of death, indicating that they may be entirely iatrogenic. Dopamine measurements for a larger series of schizophrenic and control cases (n greater than 60) show significantly increased concentrations in both the nucleus accumbens and caudate nucleus. The changes in dopamine were not obviously related to neuroleptic medication and, unlike the receptor changes, were most severe in younger patients.

Central catecholamines, cognitive impairment, and affective state in elderly schizophrenics and controls.

Central catecholamine concentrations were determined in autopsy samples from older schizophrenic and control subjects for both the hypothalamus and the nucleus accumbens. The results of these analyses and demographic variables were regressed on antemortem measures of cognitive function and mood state. In the hypothalamus, there are significant direct relationships of homovanillic acid (HVA) and 3-methoxy-4-hydroxyphenylglycol (MHPG) with depressed mood, as measured by an adaptation of the Hamilton Rating Scale for depression. In the nucleus accumbens, dopamine (DA) and MHPG had significant inverse relationships with antemortem cognitive function, as measured by an adaptation of the Mini Mental State Exam. Results in this sample indicate that after controlling for age, the catecholamine concentrations accounted for approximately 50% of the variance in the antemortem measures of mood or cognition, depending on the loci measured.

Neurotensin in projection neurons of the striatum and nucleus accumbens, with reference to coexistence with enkephalin and GABA: an immunohistochemical study in the cat.

Neurotensin-like immunoreactivity (NT-LI) was demonstrated in projection neurons of the striatum and nucleus accumbens in the cat by combining immunohistochemistry and the fluorescent retrograde neuronal labeling method. In colchicine-treated cats, many neurons with NT-LI were found in the caudate nucleus, nucleus accumbens, and putamen. Most of these neurons were medium-sized neurons with spiny dendrites. NT-LI of neuronal elements in the caudate nucleus and nucleus accumbens formed dense aggregates with irregular figures, which appeared to correspond to the striosomes of Graybiel et al. (Proc. Natl. Acad. Sci. USA 75:5723-5726, '78; Exp. Brain Res. 34:189-195, '79; Neuroscience 6:377-397, '81). Fibers with NT-LI were distributed massively to the globus pallidus and ventral midbrain regions, but not to the entopeduncular nucleus. In the ventral midbrain regions, many fine varicose fibers with NT-LI were distributed to the pars compacta and pars lateralis of the substantia nigra, ventral tegmental area, and retrorubral area. In the pars reticulata of the substantia nigra, however, fibers with NT-LI were rather sparse. Examination of consecutive sections immunostained for NT, enkephalin (Enk), GABA, and substance P (SP) revealed that 50% of neurons with NT-LI in the caudate nucleus and nucleus accumbens exhibited Enk-LI, 15% showed GABA-LI, and 5% manifested both Enk-LI and GABA-LI; no NT-positive neurons in the striatum and nucleus accumbens showed SP-LI. No morphological differences were found between NT-positive neurons with Enk-LI and/or GABA-LI and those without Enk-LI and GABA-LI. Most neurons with NT-LI in the striatum and nucleus accumbens were retrogradely labeled with True Blue injected into the globus pallidus, pars compacta and pars lateralis of the substantia nigra, and ventral tegmental area. After hemitransection severing neuronal connections between the ventral midbrain regions and the forebrain structures, fibers with NT-LI and those with Enk-LI in the ventral midbrain regions were markedly reduced in number.(ABSTRACT TRUNCATED AT 400 WORDS)

Gamma-aminobutyric acid in the medial rat nucleus accumbens: ultrastructural localization in neurons receiving monosynaptic input from catecholaminergic afferents.

Neurons containing gamma-aminobutyric acid (GABA) in the medial portion of the adult rat nucleus accumbens were characterized with respect to their ultrastructure, sites of termination, and catecholaminergic input. Antisera against GABA-conjugates and the catecholamine-synthesizing enzyme, tyrosine hydroxylase (TH), were localized within single sections by means of peroxidase-antiperoxidase (PAP) and immunoautoradiographic labeling methods. Peroxidase reaction product indicating GABA-like immunoreactivity (GABA-LI) was seen in medium-size (15-20 microns) perikarya containing either round and unindented or invaginated nuclear membranes. The cells with invaginated nuclei were few in number and usually exhibited more intense peroxidase reaction product in sections collected at the same distance from the surface of the tissue. Reaction product for GABA was also detected in proximal (1.5-3.0 microns) dendrites, axons, and terminals. Terminals with GABA-LI formed symmetric junctions on perikarya, proximal dendrites, and dendritic spines of neurons that usually lacked detectable immunoreactivity. Many of the GABAergic terminals also were apposed directly to other unlabeled terminals and to terminals exhibiting either peroxidase labeling for GABA or immunoautoradiographic labeling for TH. Many of the unlabeled terminals associated with the GABAergic axons formed asymmetric junctions on dendritic spines. From 138 TH-labeled, principally dopaminergic terminals that were examined in the medial nucleus accumbens, 4% were associated with the somata of GABAergic neurons and another 14% formed symmetric junctions with proximal dendrite showing GABA-LI. The remaining TH-immuno-reactive terminals either lacked recognizable densities or formed symmetric synapses on unlabeled dendrites and spines. A few of the unlabeled dendrites, as well as those containing GABA-LI, received symmetric synapses from both catecholaminergic and GABAergic terminals. We conclude that in the medial portion of the rat nucleus accumbens, GABA is localized to two morphologically distinct types of neurons, one or both of which receive monosynaptic input from catecholaminergic afferents, and that GABAergic terminals form symmetric synapses on other principally non-GABAergic neurons. The results also support earlier physiological evidence showing that GABA may modulate the output of other GABAergic and non-GABAergic neurons through presynaptic associations.

Somatostatin is increased in the nucleus accumbens in Huntington's disease.

Concentrations of somatostatin-like immunoreactivity (SLI) are elevated in the basal ganglia in Huntington's disease. The present study confirms these findings and, in addition, shows that concentrations of SLI are significantly elevated in the nucleus accumbens (4.04 +/- 0.66 versus 1.69 +/- 0.21 ng/mg protein in controls). This area is relatively spared pathologically and shows little atrophy in Huntington's disease. Since many patients with Huntington's disease are treated with haloperidol, we studied the effects of this drug in rats. There was a dose-dependent reduction of SLI in striatum, parietal cortex, and hippocampus. The elevated concentrations of SLI in the basal ganglia in Huntington's disease, therefore, do not appear to result from haloperidol therapy.

Striatal neurons expressing somatostatin-like immunoreactivity: evidence for a peptidergic interneuronal system in the cat.

Neurons expressing immunoreactivity to antisera against somatostatin 14 and other somatostatin-related peptides were identified in the striatum of cats and nonhuman primates. In each species, immunoreactive neurons were distributed singly and in small groups in the caudate nucleus, putamen and ventral striatum. A detailed study was made of somatostatin-positive neurons and neuropil in the caudate nucleus of the cat. First, the mean diameters and surface areas of neurons expressing immunoreactivity to somatostatin 14 were made from peroxidase-antiperoxidase stained material. Second, fluorescence immunohistochemistry was combined with retrograde labeling of striatal neurons to determine whether such somatostatin 14-positive neurons emit axons projecting out of the striatum. Third, the distributions of neurons and neuropil expressing immunoreactivity to somatostatin 14 or somatostatin 28 (1-12) were plotted in relation to the locations of acetylcholinesterase-poor zones ("striosomes") visible in adjoining sections. The morphometric analysis suggested that somatostatin 14-positive neurons in the caudate nucleus form a single population of medium to medium-large neurons having mean diameters of 20 micron and mean surface areas of 154 micron2. The retrograde tracer study suggested that these somatostatin 14-positive neurons are interneurons. Injections of fast blue into all of the known targets of striatofugal fiber projections failed to label somatostatin 14-positive neurons save in a few instances (less than 0.3% of more than 4000 neurons) in each of which labeling was equivocal. Analysis of the distribution of somatostatin-positive neurons and neuropil in the striatum demonstrated that both observe striosomal ordering. Somatostatin immunoreactive neuropil was dense outside and weak inside identified striosomes, and most immunoreactive neurons lay outside. Often somatostatin-positive neurons lay beside, and sometimes striosomes partly rimmed them. The processes of such neurons tended to run along the borders of the striosomes without crossing them, but occasionally single processes and rarely entire dendritic trees crossed from one compartment to the other. These results suggest that, in the striatum of the cat, somatostatin is present: (1) in fibers organized according to the compartmental distribution already recognized for other neurochemical compounds in the striatum as well as for its afferent and efferent systems, and (2) in interneurons, mostly present in the extrastriosomal matrix, but also located near striosomes, where they could serve as interfaces between the striosomes and extrastriosomal matrix.

Behavioral and neurochemical effects of neurotensin microinjection into the ventral tegmental area of the rat.

The ventral tegmental area of the rat brain has been shown to possess high densities of neurotensin- and dopamine-containing neuronal perikarya. We recently demonstrated that microinjection of neurotensin into the ventral tegmental area produces behavioral hyperactivity similar to amphetamine-induced increase in exploratory behaviors, but lacking stereotypies. In this study, we report that the threshold dose for neurotensin-induced hyperactivity is 0.10-0.25 micrograms neurotensin/side. Either intracerebroventricular injection of haloperidol (5.0 micrograms/lateral ventricle) or destruction of the mesolimbic dopamine system by 6-hydroxydopamine abolishes the behavioral hyperactivity produced by intraventral tegmental injection of neurotensin (2.5 micrograms/side). Using high pressure liquid chromatography with electrochemical detection, we show that neurotensin injection into the ventral tegmental area increases the concentration of dopamine metabolites, 3,4-dihydroxyphenylacetic acid and homovanillic acid in the nucleus accumbens and olfactory tubercles, but not in the striatum. This effect is especially profound in the nucleus accumbens where the threshold dose is less than 0.025 micrograms/side. The ratio of 3,4-dihydroxyphenylacetic acid to dopamine increased in the nucleus accumbens and olfactory tubercles in a dose-dependent fashion (0.025 microgram-2.50 micrograms/side). Neurotensin-induced behavioral hyperactivity correlates positively with neurotensin-induced changes in the ratio of 3,4-dihydroxyphenylacetic acid to dopamine. This study indicates that neurotensin acts in the ventral tegmental area to activate the mesolimbic dopamine system. Further, this activation produces behavioral hyperactivity characterized by an increase in exploratory behaviors. The fact that both immunoreactive neurotensin and neurotensin receptors are found in high concentration in the ventral tegmental area supports the possible physiological significance of this peptide-catecholamine interaction.

Cell clusters in the nucleus accumbens of the rat, and the mosaic relationship of opiate receptors, acetylcholinesterase and subcortical afferent terminations.

The nucleus accumbens is located ventromedially in the mammalian neostriatum. Nissl- and myelin-stained material from the rat shows that the internal organization of the accumbens features clusters of cells occupying myelin-poor regions. These cell clusters served as basic morphological units against which several other histological features were examined. Markers for opiate receptors, acetylcholinesterase and subcortical afferent termination patterns reveal a mosaic heterogeneity in register with the cell clusters. Specifically, [3H]naloxone binds densely, acetylcholinesterase stains weakly and [3H]amino acids, anterogradely transported from the thalamic paraventricular, paratenial and central medial nuclei and from the ventral tegmental area, label termination-poor zones--all in patterns which correspond to the cell clusters. Details of this fit were provided by Golgi analysis of the spread of cell cluster dendrites. The restriction of dendrites to cell cluster territory, together with the sharply defined edges of opiate receptor and thalamic tract termination patterns, suggests that some connections are excluded from the clusters, and others terminate almost exclusively within their domain. Dopamine fluorescence is weak in the cell cluster areas, supporting the idea that projections from dopaminergic cells in the ventral tegmental area avoid cell clusters. Though certain extrinsic afferent projections are excluded from the cell clusters, it is argued that inputs from nearby striatal enkephalinergic neurons are preferentially received. Taken together, these findings suggest that the cell clusters are way-stations devoted to intrinsic information processing. It is speculated that these concepts can be extended to chemically similar arrangements in the caudate-putamen, which lacks a cytoarchitectural unit as distinct as the cell cluster.

Brain dopamine autoreceptors in aging rats.

The function of dopamine (DA) autoreceptors is evaluated in vivo in striatum and mesolimbic regions of young adult (4 months), mature (14 months) and old (26 months) male Wistar rats. gamma-Butyrolactone (GBL)-induced dihydroxyphenylalanine (DOPA) accumulation in rats also treated with an inhibitor of aromatic L-aminoacid decarboxylase was used to determine the presence of synthesis-modulating nerve terminal autoreceptors while its reversal with apomorphine served as an index of autoreceptor stimulation. GBL-induced DOPA accumulation in striatum is very high at all three ages (130-150% increase in comparison with controls) as is its reversal by apomorphine (65-80% decrease in comparison with GBL alone). In mesolimbic regions, GBL has much less effect than in striatum (31% rise at 4 and 26 months, 12% rise at 14 months), but apomorphine's effect is of the same order of magnitude (down 60-80%). The conclusion can be drawn that aging does not significantly affect DA autoreceptor function in striatum and mesolimbic areas.

The effect of repeated administration of antidepressant drugs on the thyrotropin-releasing hormone (TRH) content of rat brain structures.

The present study investigated the effect of repeated treatment with the antidepressant drugs imipramine, amitryptyline, citalopram and mianserin (10 mg/kg PO, twice daily for 14 days) on levels of thyrotropin-releasing hormone (TRH) in several brain structures (cerebral cortex, amygdala + pyriform cortex, hippocampus, nucleus accumbens, striatum and hypothalamus) of the rat. Amitriptyline caused a marked increase in the TRH content in the striatum and nucleus accumbens. Citalopram and mianserin produced a smaller but significant increase in the TRH content in the striatum only, while imipramine did not significantly affect the TRH concentrations in any of the brain structures. None of the antidepressant drugs administered acutely significantly affected the TRH concentrations in the nucleus accumbens or the striatum. These results indicate that changes in brain TRH induced by antidepressant drugs are not related to their therapeutic activity.

Conditioning of pre- and post-synaptic behavioural responses to the dopamine receptor agonist apomorphine in rats.

We investigated whether pharmacological effects of the dopamine agonist apomorphine can be conditioned by establishing an association of apomorphine administration with exteroceptive cues. Apomorphine was repeatedly administered and subsequently, the rat was put into a test cage and exposed to an acoustic and an olfactory stimulus ("conditioned rats"). Control animals ("pseudoconditioned" rats) were treated with the same pharmacological schedule of apomorphine not temporally associated with the stimuli. On the test day, both groups were injected with saline and exposed to the stimuli described. The stereotyped behaviour produced by large doses of apomorphine (0.5 or 2.0 mg/kg SC), namely sniffing, licking and gnawing, could be conditioned in a pronounced way. During the conditioning period, a change in the stereotypies was observed with regard to the time-course (earlier occurrence) and to the character of the stereotypies (from sniffing to licking and gnawing), when 0.5 mg/kg apomorphine was used, but not with the dose of 2.0 mg/kg. The conditioned responses showed a relatively uniform distribution during the observation period with some increase towards the end of the observation period. Some signs produced by a low dose of apomorphine (0.07 mg/kg SC), namely hypomotility and ptosis, but not yawning, could also be conditioned, although in a less pronounced way. An intermediate dose of apomorphine (0.18 mg/kg SC) produced both signs observed after large doses and those observed after a small dose, occurring alternatingly. Both types of signs could be conditioned using this dosage. Conditioning did not alter striatal or mesolimbic dopamine turnover.(ABSTRACT TRUNCATED AT 250 WORDS)

Cholecystokinin in intracerebral transplants.

Fetal mesencephalic tissue containing dopamine and cholecystokinin-immunoreactive neurons was grafted to the striatum of adult host rats, either as solid pieces of tissue or as cell suspensions. The dopaminergic innervation of the striatum was previously ablated unilaterally by neurotoxin. Immunohistochemical analysis using antibodies to cholecystokinin and tyrosine hydroxylase was performed at least 8 weeks after grafting. Neurons immunoreactive to tyrosine hydroxylase or cholecystokinin, as well as neurons immunoreactive to both compounds were found in the transplants. In the solid tissue grafts the proportions of neurons exhibiting either CCK- or tyrosine hydroxylase-like immunoreactivity to neurons exhibiting both immunoreactivities were similar to those seen in intact ventral mesencephalon. This suggests that these neurons are able to maintain and express their transmitter phenotypy when transplanted to an ectopic location. An extensive outgrowth of fibers containing tyrosine hydroxylase-like immunoreactivity, but apparently lacking cholecystokinin-like immunoreactivity, was observed in the host striatum. Cholecystokinin-immunoreactive fibers were found in a narrow zone immediately adjoining the graft. The results suggest the possibility that growth-regulating mechanisms in the denervated host striatum selectively favor the ingrowth of fibers from the appropriate dopaminergic neuronal subset.

Evidence for cholecystokinin-dopamine receptor interactions in the central nervous system of the adult and old rat. Studies on their functional meaning.

Evidence has been presented for the existence of interactions between CCK and DA receptors both in striatal and limbic membranes. A similar type of modulation by CCK-8 of DA receptors also exists after chronic neuroleptic treatment indicating that supersensitive DA receptors are also modulated by this peptide. As seen from simulation curves, CCK-8 increases the binding of [3H]DA agonists and reduces the binding of [3H]DA antagonists in striatal membranes, suggesting that CCK-8 may increase striatal DA transmission. Results of this type may underlie some of the non-neuroleptic effects of CCK-8. In the aged brain, the ability of CCK-8 to modulate DA antagonist binding sites is changed such that the binding of [3H]DA antagonists is increased. Thus, in the aged brain, receptor-receptor interactions may be altered, leading to a derangement of heterostatic mechanisms (mechanisms changing chemical transmission without interfering with synaptic homeostasis). It was also demonstrated that during aging there is a preferential disappearance of CCK-like immunoreactivity versus TH immunoreactivity in the nigral DA neurons, especially in the medially located nigral DA cells; furthermore, co-existence in the TH/CCK co-storing terminals in the nucleus accumbens was reduced during aging. Such alterations should also lead to changes in heterostatic regulation because the CCK co-modulation line controlling the DA receptors may be preferentially affected.

Simultaneous monitoring of 3,4-dihydroxyphenylacetic acid (DOPAC) and 5-hydroxyindoleacetic acid (5-HIAA) levels in the brains of freely moving rats by differential pulse voltammetry technique.

Differential pulse voltammetry with a newly devised carbon fiber electrode was used to study the nature of striatal electrochemical signals. Voltammograms recorded from the striatum of unanesthetized rats usually yielded the combined oxidation peak (1 + 2) and peak 3. Peaks 1 and 2 could be separated by eliminating peak 1 for ascorbate by electrochemical oxidation in the brain to allow clear monitoring of peak 2 at + 120 mV for catechols and peak 3 at + 270 mV for indoles. The changes in the oxidation potentials and the amplitudes of peaks 2 and 3 corresponded to those of 3,4-dihydroxyphenylacetic acid (DOPAC) and 5-hydroxyindoleacetic acid (5-HIAA) in vivo because: the oxidation potentials of peak 2 (+ 120 mV) and peak 3 (+ 270 mV) coincided with those of DOPAC and 5-HIAA in vitro; increases in the heights of peaks 2 and 3 were observed after micro-infusion of DOPAC and 5-HIAA, respectively, into the striatum; and peak 2 height increased after injection of haloperidol and gamma-butyrolactone and decreased after amphetamine and pargyline, while peak 3 amplitude increased following injection of gamma-butyrolactone, probenecid and 5-hydroxytryptophan and decreased after pargyline. Thus, the in vivo voltammetry method enabled simultaneous and stable monitoring of the dynamic changes in DOPAC and 5-HIAA levels in the brains of freely moving rats.

Failure of chronic haloperidol treatment to alter levels of cholecystokinin in the rat brain striatum and olfactory tuberclenucleus accumbens area.

We have studied the effect of chronic haloperidol (HAL) treatment on CCK-8 levels in two rat brain regions. HAL administration using two different protocols, daily injections and infusion with subcutaneously implanted minipumps, did not produce any significant changes in CCK-8 levels in the striatum or olfactory tubercle-nucleus accumbens area.

Apomorphine affects cholecystokinin content via preferentially D1 or D2 dopamine receptor according to the regions of the rat brain.

Cholecystokinin octapeptide-like immunoreactivity (CCK-8IR) was measured in several regions of the rat brain after the intraperitoneal administration of apomorphine, SKF-38393 (D1 agonist), LY-171555 (D2 agonist). In the medial prefrontal cortex and striatum, apomorphine and SKF 3839 decreased CCK-8IR. In the anterior and posterior nucleus accumbens, on the other hand, the inhibitory effect of apomorphine was mimicked by LY-171555. These results suggest that apomorphine affects CCK-8IR via either the D1 dopamine (DA)-receptor or D2 DA-receptor according to the brain region.

Brain dopamine receptor levels elevated in canine narcolepsy.

Concentrations of dopamine D2 receptors in discrete brain areas differed significantly between dogs with the genetically transmitted form of narcolepsy, and age- and breed-matched controls. D2 receptors were assayed and quantified with Scatchard analysis using [3H]spiperone. Receptor densities in the nucleus accumbens, rostral caudate, and amygdala were consistently higher in narcoleptic animals. In amygdala, dopamine receptor abnormalities were associated with elevated dopamine and 3,4-dihydroxyphenylacetic acid concentrations, but no change in 3-methoxytyramine or homovanillic acid concentrations. These data indicate mesolimbic system involvement in canine narcolepsy and point to impaired dopamine release as a possible etiologic factor.

Dopamine D-1 receptors in the parkinsonian brain.

Dopamine D-1 receptors were analyzed in the caudate nucleus, putamen, pallidum, substantia nigra and nucleus accumbens in 20 patients with Parkinson's disease and in 18 age-matched controls by the binding of [3H]flupenthixol. The binding was decreased in the substantia nigra in those parkinsonian patients who were not treated with levodopa. A significantly increased number of D-1 receptors was found in the putamen of patients with Parkinson's disease, especially in those who were treated with levodopa. The increased binding of [3H]flupenthixol was most prominent in those six parkinsonian patients who still had therapeutic response to levodopa. In addition, orofacial dyskinesias were seen in three of these patients. The results of this study indicate that there may be denervation supersensitivity of striatal neurons and also a loss of striatonigral neurons in Parkinson's disease.

The masking of amine accumulation by catecholamine depletion.

6-Hydroxydopamine (2 microliter of 8 micrograms/microliter) was injected bilaterally into the lateral hypothalamus of male Sprague-Dawley rats to produce depletion of forebrain terminal fields and an accumulation of amines proximal to the site of injection. Two additional groups of animals were injected with either vehicle or were food and water intake-matched to those receiving 6-hydroxydopamine. Motor performance, food and water intake and body weight were measured in all animals for 2 days before and 6 days after injection. Animals were then sacrificed and brain tissue was prepared for biochemical assay or fluorescence histochemistry. The area of hypothalamic tissue proximal to 6-hydroxydopamine injection, that which contains the amine accumulation, was sectioned from the surrounding tissue with a biopsy punch and assayed for noradrenaline and dopamine content. The nucleus caudatus-putamen, basomedial hypothalamus, and tissue containing the olfactory tubercle and accumbens nucleus were also assayed. Fluorescent histochemical examination of tissue showed that in addition to the depletion of catecholamines in various terminal fields there was also an increase in the fluorescent amine accumulation proximal to the injection site in the impaired animals. This accumulation was not detected with the biochemical assay and is probably due to the occurrence of a masking effect by adjacent depletions. A significant rise in noradrenaline levels was seen in the basomedial hypothalamus of intake-matched controls. However, this too was not detected in 6-OHDA-treated animals and was probably due to masking by adjacent depletions in these areas.(ABSTRACT TRUNCATED AT 250 WORDS)