Age-related changes on monoamine turnover in hippocampus of rats

After pargyline treatment the turnover rates of dopamine (DA), noradrenaline (NA), 3,4-dihydroxyphenylacetic acid (DOPAC), serotonin (5-hydroxytryptamine (5-HT) and 5-hydroxy-3-indolacetic acid (5-HIAA) has been measured in control and aged hippocampus of the rats. In addition, the tyrosine hydroxylase (TH) activity and monoamine oxidase-A and monoamine oxidase-B activities have also been studied. The TH activity did not change in aged hippocampus as compared to controls. The monoamine oxidase-B:monoamine oxidase-A ratio increased in 26-month-old rats compared with controls. The turnover of DA, DOPAC and NA did not show significant changes while 5-HT synthesis, 5-HT accumulation rate and 5-HIAA turnover increased in aged rats. Serotonin fibers showed morphological dissimilarities between the hippocampus of young and aged rats using immunocytochemistry techniques. In aged rats aberrant serotoninergic fibers mainly appear in the molecular layer of the dentate gyrus and moleculare of the hippocampal CA1. It is suggested that the aberrant morphology of 5-HT fibers may reflect the local degeneration of serotoninergic hippocampal afferents during aging. Increase of 5-HT turnover in aged might be a signal of degeneration.     

丘脑底核电刺激对猴偏侧帕金森病纹状体神经递质的影响

目的 探讨应用微透析技术在慢性STN—DBS对纹状体细胞外液多巴胺及代谢产物的影响。方法 选择已经成功安装脑深部刺激电极的偏侧PD猕猴模型2只，分别在打开脉冲发生器前、后的不同时间点取样（开机后8h、1周、1个月、2个月）。应用高效液相电化学方法检测开机前后的尾状核和壳核细胞外液的多巴胺（DA）及其代谢产物含量。结果 电极侧壳核和尾状核的DA在开机后8h、1周、1个月、2个月相应地分别较各自开机前的DA含量增高了39％、91％、111％、114％和31％、91％、106％、102％（P〈0．05）。电极侧壳核和尾状核HVA／DA在开机后8h分别较各自开机前增高了186％和91％（P〈0．05），而开机后1周、1个月、2个月HVA／DA较开机前无明显变化（P〉0．05）。电极侧的多巴胺周转率在开机后的各时间点均显著低于非电极侧（P〈0．01）。结论 STN—DBS可有效的改善猴偏侧PD模型的症状，应用微透析取样技术结合高效液相色谱测，定法发现在给予有效电刺激后可增加刺激侧纹状体细胞外液的多巴胺及其代谢产物含量。为STN—DBS治疗帕金森病提供理论依据。     

In vivo comparison of the regulation of releasable dopamine in the caudate nucleus and the nucleus accumbens of the rat brain

In vivo voltammetry has been used to measure the release of dopamine evoked by electrical stimulation of the medial forebrain bundle (MFB). Simultaneous measurements have been made with voltammetric-sensing electrodes ipsilateral to the stimulating electrode in the nucleus accumbens and the caudate nucleus of the anesthetized rat. During the stimulation, the species observed in both regions is voltammetrically identical to dopamine. Further evidence for the identity of dopamine is provided by anatomical, physiological, pharmacological, and postmortem data. Postmortem analysis of these brain regions after a single stimulation demonstrates that dopamine levels are unchanged, while dihydroxyphenylacetic acid (DOPAC) levels are increased in both regions. Systemic application of synthesis inhibitors results in a decrease in evoked release for each brain region. Amfonelic acid results in a restoration of stimulated release after synthesis inhibition. Evoked release is affected differently by pargyline in the two brain regions. The evoked release of dopamine is significantly elevated in the nucleus accumbens as a result of pargyline administration, but similar effects are not seen in the caudate nucleus. Tissue levels of dopamine are increased in both brain regions by pargyline, but the increase is significantly greater in the accumbens. Electrolytic lesions of the striatonigral pathway or systemic administration of picrotoxin eliminates the pargyline-induced difference in evoked release of dopamine. Amphetamine causes a reduction in stimulated release in the caudate nucleus with little effect on that observed in the nucleus accumbens.(ABSTRACT TRUNCATED AT 250 WORDS)     

Synthesis of catecholamines from [H]tyrosine in brain during the performance of operant behavior

Changes in the synthesis rates of dopamine (DA) and norepinephrine (NE) in brain were found to accompany the performance of positively reinforced operant behavior in rats. Catecholamine synthesis rates were estimated at short time intervals after the intraventricular injection of [³H]tyrosine with use of a conversion index which expressed the levels of [³H]DA or [³H]NE accumulated in various brain regions as a function of the specific activity of [³H]tyrosine. In rats lever pressing on a fixed ratio 5 schedule of water reinforcement, the DA conversion index in the caudate putamen was 66% higher than in control rats but was not different from control values in the mesolimbic area and hypothalamus. The NE conversion index in operant-performing animals was 48% higher in the hypothalamus than in controls but was unchanged in the mesolimbic area, telencephalon and brainstem. The changes in the CA conversion indices seen during operant performance were associated with increases in the brain levels of [³H]DA or [³H]NE, but were not accompanied by alterations in either the specific activity of [³H]tyrosine or the endogenous levels of catecholamines. The relative increment in the DA conversion index seen in the caudate putamen of operant-performing rats was directly proportional to the number of lever presses emitted following [³H]tyrosine administration. These findings indicate that the performance of operant behavior is associated with increases in rate of catecholamine synthesis within select populations of central neurons.     

Regional changes in brain dopamine and serotonin metabolism induced by conditioned circling in rats: effects of water deprivation, learning and individual differences in asymmetry

Rats were trained, using water reinforcement, to turn in circles (rotation) during 1 h daily test sessions. After achieving criterion performance (100 full turns per hour) for at least 10 consecutive sessions, rats were sacrificed 20 min after starting a session and levels of dopamine, DOPAC (3,4-dihydroxyphenylacetic acid), serotonin, and 5-HIAA (5-hydroxyindoleacetic acid) were assayed in nigrostriatal (corpus striatum), mesolimbic (nucleus accumbens) and mesocortical (medial prefrontal cortex) brain regions. Other control groups of rats were comparably water deprived or satiated at the time of sacrifice. Although, as previously reported, evidence of 'two populations' of rats was again apparent with respect to the relationship between direction of spontaneous turning and asymmetry in striatal dopamine levels, there were no lateralized effects of operant rotational training on striatal dopamine and DOPAC levels nor on the DOPAC/dopamine ratio. There were, however, bilateral neurochemical effects of both rotational training and water deprivation in striatum: an increase in the 5-HIAA/serotonin ratio in both sexes was attributable to learning whereas an increase in the DOPAC/dopamine ratio in males was attributed to water deprivation. A bilateral decrease in the DOPAC/dopamine ratio in the mesolimbic and mesocortical regions of both sexes was also induced by water deprivation. The only lateralized neurochemical changes associated with learning to rotate in the operant task occurred in the medial prefrontal cortex: in both sexes, dopamine levels were higher in the ipsilateral than in the contralateral cortex and the DOPAC/dopamine ratio was greater in the contralateral than in the ipsilateral cortex.(ABSTRACT TRUNCATED AT 250 WORDS)     

The metabolism of dopamine in the median eminence reflects the activity of tuberoinfundibular neurons

The purpose of the present study was to characterize the metabolism of dopamine (DA) in tuberoinfundibular (TI) neurons terminating in the median eminence and to examine the effects of procedures that alter the synthesis and turnover of DA in these neurons on the concentrations of dihydroxyphenylacetic acid (DOPAC) in the median eminence. The DA uptake inhibitor nomifensine (25 mg/kg, i.p.; 30 min) failed to alter median eminence DOPAC concentrations indicating that very little released DA is recaptured and metabolized by TIDA neurons. Within 5 min following the administration of the monoamine oxidase inhibitor pargyline (50 mg/kg, i.v.) median eminence DOPAC concentrations declined to 15% of control demonstrating that this metabolite has a high turnover rate and is rapidly removed from the median eminence. Median eminence DOPAC concentrations in diestrous female rats, whose TIDA neuronal activity is higher than in the male, were two-fold greater than in male rats. Prolactin (10 micrograms/rat, i.c.v.; 12 h), which increases TIDA neuronal activity, produced a corresponding increase in median eminence DOPAC concentrations in male rats. Restraint stress (30 min), which decreases TIDA neuronal activity, produced a corresponding decrease in median eminence DOPAC concentrations in diestrous female rats. The results from the present study suggest that DOPAC concentrations in the median eminence can be used as an index of TIDA neuronal activity.     

Effects of monoamine uptake inhibitors given early postnatally on monoamines in the brain stem,caudate/putamen and cortex,and on dopamine D1 and D2 receptors in the caudate/putamen

Summary Rats were treated with desipramine 5mg/kg, nomifensine 10mg/kg, zimelidine 25 mg/kg or with 0.9% sodium chloride once a day during the second and third weeks after birth, and brain stem, caudate/putamen and cortical monoamines, and caudate/putamen dopamine D₁ (³[H]SCH 23390) and D₂ (³[H]spiroperidol) receptor binding were measured when rats were at two months of age. In the brain stem, the concentration of 3-methoxy-4-hydroxy-phenyl glycol was increased in nomifensine rats and the ratio of 5-hydroxyindoleacetic acid to 5-hydroxytryptamine was increased in zimelidine rats. In the caudate/putamen, the concentrations of 3,4-dihydroxyphenylacetic acid and homovanillic acid and the ratio of homovanillic acid to dopamine were increased in desipramine rats; neither³[H]SCH 23390 nor³[H]spiroperidol binding were affected by any of the three monoamine uptake inhibiting antidepressants studied. In the cortex, the ratio of 5-hydroxyindoleacetic acid to 5-hydroxytryptamine was increased in desipramine and zimelidine rats. The findings suggest that desipramine but not nomifensine increases the metabolism of dopamine in the caudate/ putamen and nomifensine but not desipramine increases the metabolism of norepinephrine in the brain stem, and furthermore that the metabolism of serotonin is affected by desipramine as well as by zimelidine. It is possible that also treatment of women with these drugs during late pregnancy causes long-lasting changes in the brain of human fetus.     

Huntington chorea is not associated with hyperactivity of nigrostriatal dopaminergic neurons: studies in postmortem tissues and in rats with kainic acid lesions

We estimated dopamine release postmortem in the neostriatum of patients with Huntington disease (HD) and in controls. In HD, dopamine levels were unchanged in caudate and elevated in putamen, but homovanillic acid (HVA) and the ratio HVA:dopamine were unaltered in both nuclei. When rats were injected with kainic acid (an experimental model of HD), dopamine levels in striatum remained unchanged 2 to 30 days postoperatively; HVA and 3,4-dihydroxyphenylacetic acid (DOPAC) increased significantly from 2 to 18 days after injections but returned to normal levels later. These findings suggest that the nigrostriatal projection adapts to loss of striatal neurons that normally influence dopamine release and is not hyperactive in HD chorea.     

Simultaneous determination of the formation rate of dopamine and its metabolite 3,4-dihydroxyphenylacetic acid (DOPAC) in various rat brain areas

Administration of the MAO-inhibitor pargyline resulted in an increase of dopamine (DA) and an exponential decrease of the metabolite 3,4-dihydroxyphenylacetic acid (DOPAC) in arious rat brain areas. From these curves the rate of formation of DA and the rate of removal of DOPAC were calculated, within one experiment, for the striatum, tuberculum olfactorium and frontal cortex. When the accumulation rate of 3-methoxytyramine was taken into account it appeared that the rate of DA formation was in good agreement with the rate of DOPAC removal in the brain areas studied. The contribution of the DA formation to the synthesis of noradrenaline in the frontal cortex appeared negligible. The earlier reported rapid rise of strittal DA levels after administration of aminotetralin-derived DA agonists suggests that the synthesis rate of the biogenic amine is higher than its rate of metabolism. It appeared from the present study that an increased rate of synthesis of DA induced by the DA agonists was responsible for this discrepancy.     

Dopamine and homovanillic acid concentrations in striatal and limbic regions of human brain

In an attempt to further define the dopaminergic nature of the limbic nucleus accumbens from the morphologically similar striatal caudate and putamen, the levels of dopamine (DA), homovanillic acid (HVA), and HVA/DA ratios, an index of dopamine turnover, were measured in these three structures of human brain. The levels of dopamine in the accumbens (2.49 ng/mg), caudate (2.39 ng/mg), and putamen (3.00 ng/mg) were similar. The homovanillic acid concentration in the accumbens (7.44 ng/mg) and putamen (6.54 ng/mg) were comparable, while its concentration was considerably lower in the caudatae (3.61 ng/mg). The most striking difference between the limbic accumbens and the striatum was observed in the HVA/DA ratio. This index of turnover was significantly higher in the accumbens (3.64) when compared to the caudate (1.80), and was 59% higher than that found in the putamen (2.53). The data provide evidence for differences in dopamine activity in the mesolimbic versus the nigrostriatal pathways.     

Increased dopamine turnover in the putamen after MPTP treatment in common marmosets

The differences in dopamine turnover rate between the putamen and the caudate nucleus in the striatum lesioned by a neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) were studied in the common marmoset, a small New World monkey. Systemic administration of MPTP damaged equally and dose-dependently nigrostriatal dopaminergic neurons projecting both to the caudate nucleus and the putamen. The compensatory increase of dopamine turnover, however, occurred more prominently in the putamen than in the caudate. The neural connection and function of the caudate nucleus and the putamen have been differentiated anatomically or physiologically. The compensatory increase of dopamine turnover rate is another different aspect of functions between the caudate nucleus and the putamen. Dopaminergic neurons projecting to the putamen showed more prominent cell loss than those projecting to the caudate in Parkinson's disease or related disorders. The selective augmented turnover rate of lesioned dopaminergic neurons might be, at least partly, involved with selective degeneration of nigrostriatal neurons projecting to the putamen.     

Monoamine oxidase-dependent metabolism of dopamine in the striatum and substantia nigra of l-DOPA-treated monkeys

The effects of monoamine oxidase (MAO) inhibitors on the metabolism of dopamine synthesized from exogenous l-DOPA were investigated in the striatum and substantia nigra of squirrel monkeys. Administration of a single dose of l-DOPA (methyl ester, 40 mg/kg, i.p.) caused a significant increase in the levels of dopamine, 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) and in the DOPAC/dopamine ratio in the putamen, caudate and substantia nigra. These changes were more pronounced in the substantia nigra than in the striatum and within the striatum of l-DOPA-treated monkeys, levels of dopamine and its metabolites were higher in the putamen than in the caudate nucleus. When l-DOPA treatment was preceded by the injection of clorgyline or deprenyl at a concentration (1 mg/kg) which selectively inhibited MAO A or MAO B, respectively, striatal dopamine was increased while the striatal DOPAC and HVA levels and DOPAC/dopamine ratio were significantly reduced as compared to the values obtained with l-DOPA alone. The two MAO inhibitors also counteracted the increase in the DOPAC and HVA levels and DOPAC/dopamine ratio induced by l-DOPA in the substantia nigra. Thus, both MAO A and MAO B contribute to the metabolism of dopamine when higher levels of this neurotransmitter are generated from l-DOPA in the squirrel monkey. The extent of reduction of dopamine catabolism (as assessed by the decrease in DOPAC and HVA levels) in the striatum and substantia nigra was similar with clorgyline and deprenyl even if the ratio MAO A/MAO B was approximately 1 to 10. This indicates that, though catalyzed by both MAO A and MAO B, dopamine deamination following treatment with l-DOPA preferentially involves MAO A.     

Chronic haloperidol-induced changes in regional dopamine release and metabolism and neurotensin content in rats

Chronic neuroleptic administration has previously been shown to alter in vivo measures of dopaminergic function and lead to regionally selective increases in neurotensin levels. In the current study, female rats were administered chronic haloperidol for 6 months via subcutaneous silastic implants. After 24 weeks of administration, microdialysis probes were inserted into the lateral caudate putamen and the medial prefrontal cortex. Basal samples were collected prior to infusion of a high K⁺ concentration (100 mM KCI). Extracellular concentrations of dopamine, 3,4-dihydroxyphenylacetic acid, homovanillic acid, and 5-hydroxyindoleacetic acid were assessed using HPLC. Chronic haloperidol-treated rats showed increased basal dopamine metabolite levels in the caudate putamen and an altered response to the effects of high K⁺ on 3,4-dihydroxyphenylacetic acid; no significant differences were seen with other analytes in the caudate putamen. Although basal concentrations were not different between groups in the prefrontal cortex, haloperidol-treated rats showed a significant attenuation of response to the effects of high K⁺ infusion on dopamine metabolite concentrations. Radioimmunoassay measurement of tissue neurotensin content showed highly significant elevations of neurotensin concentrations in the caudate putamen and nucleus accumbens, but not in other brain regions analyzed. These results suggest a confluence of altered dopamine and neurotensin function in the caudate putamen which may be related to motor side effects of haloperidol, whereas changes in prefrontal dopamine function are not associated with altered neurotensin levels.     

Differential responses in central dopaminergic activity induced by apomorphine in IPL nude rat

The IPL nude rat, derived by spontaneous mutation from the Sprague-Dawley strain, presents alterations in the prolactin synthesis and secretion due to an increased dopaminergic inhibition. However, there are no reports concerned to central dopamine activity. The corpus striatum is a brain area involved in the development of stereotyped behavior after the activation of mesolimbic and/or nigro-striatal dopamine pathways. In order to identify possible mesolimbic and/or nigro-striatal dysfunctions in the IPL nude rat, we study the spontaneous oral behaviors and the effects of apomorphine-induced dopaminergic activation on stereotyped behavior and neurochemical changes. Males from both strains were injected with saline or apomorphine (2 and 5 mg/kgs.c.) and evaluated during 30 min in a stereotypes oral tests. The corpus striatum and nucleus accumbens were used to measure dopamine (DA), 3,4-dihydroxyphenylalanine (DOPA) and 3,4-dihydroxyphenylacetic acid (DOPAC) by HPLC. The concentrations were expressed as synthesis rate (DA/DOPA) and turnover rate (DOPAC/DA). We observed that the spontaneous gnaw movements were significantly different between the untreated IPL nude and Sprague-Dawley (SD) rats. Apomophine injection decreased the amount of stereotyped gnawing in IPL nude rats at the two doses used, but it induced an increase in SD rats. Apomorphine also caused an enhancement in the number of biting and sniffing without modifying the licking behavior. In addition, modifications of the dopaminergic activity were also observed. Synthesis rate in the striatum of IPL nude rats was higher than in SD rats after the injection of saline. Apomorphine caused a reduction of the synthesis rate in both strains. Turnover rate was significantly lower in the striatum of IPL nude rats than in the SD rats injected with saline. Apomorphine caused an increase in the turnover rate in both strains. Contrary to observed in the striatum, the 2 mg/kg dose of apomorphine caused a significant increase in the DA synthesis rate in nucleus accumbens, while 5 mg/kg decrease it in both strains. The DA turnover rate in the same area was lower in IPL nude than in SD rats after saline injection. Apomorphine enhances the DA turnover rate in both strains. We conclude that the modifications of the oral spontaneous and induced stereotypical patterns observed in the IPL nude rats could be related to the differential responses in dopaminergic activity in the two brain areas examined.     

Presynaptic dopaminergic function is largely unaltered in mesolimbic and mesostriatal terminals of adult rats that were prenatally exposed to cocaine

Fast-scan cyclic voltammetry in brain slices and postmortem tissue content assessment were used to evaluate presynaptic dopaminergic function in the caudate putamen and nucleus accumbens of adult male rats (180+ days old) that were prenatally treated with either cocaine or saline. Experiments were carried out to test whether there were differences in dopamine release, reuptake, autoreceptor function or the tissue levels of dopamine and its metabolites between cocaine- and saline-exposed rats. We report that presynaptic dopaminergic function remains largely intact in adult rats that were prenatally exposed to cocaine. The ability of terminals in the caudate putamen and nucleus accumbens to release and regulate dopamine is unaltered by prenatal cocaine exposure. However the tissue content of dopamine in the caudate putamen was decreased, representing a diminution in the dopamine storage pool. We conclude, therefore, that behavioral changes that have previously been observed in rats that were prenatally exposed to cocaine are not mediated through alteration of presynaptic dopaminergic mechanisms in these brain regions.     

Determination of neurotransmitter release into the caudate nucleus during convulsions induced by pentylenetetrazole using in vivo differential pulse voltammetry

In vivo differential pulse voltammetry using an electrochemically treated carbon fiber electrode was applied to the investigation of the in vivo release of indoleamine and catecholamine within the caudate nucleus of freely moving and immobilized rats during convulsions induced by pentylenetetrazole (PTZ). Two distinct oxidation peaks, on at 130 mV (3,4-dihydroxyphenylacetic acid (DOPAC] and the other at 300 mV (5-hydroxyindoleacetic acid), were observed in voltammograms obtained from the caudate nucleus. In the caudate nucleus of freely moving rats, the in vivo oxidation current that peaked at 300 mV showed almost no change during and after tonic convulsions induced by 60 mg/kg of PTZ i.p. During tonic convulsions, the amplitude of the DOPAC oxidation peak significantly decreased to 75% of the peak height recorded prior to the injection of PTZ, and the minimum lasted for about 30 min; then the mean curve slowly recovered to the control level within 60 min. These results suggest that the release of dopamine (DA) in the caudate nucleus of freely moving rats decreased during tonic convulsions induced by PTZ. In another experiment, the EEGs of immobilized rats were recorded simultaneously, and the changes in the EEG pattern were used as an index of convulsion. In voltammograms from the caudate nucleus of immobilized rat, the peak height of the 130-mV oxidation potential significantly increased during ictal seizures. The increase lasted for 3-6 min after the ictal seizures. The severe electrical activity of the brain during ictal seizures interfered with the recording of some voltammograms.(ABSTRACT TRUNCATED AT 250 WORDS)     

Modification of inherent and drug-induced dopaminergic activity after exposure to benzo(alpha)pyrene

The aim of this study was to investigate the effect of benzo(alpha)pyrene (B(alpha)P), a representative polycyclic aromatic hydrocarbon (PAH), on dopaminergic activity in brain. (B(alpha)P) altered dopaminergic activity in discrete regions of the rat brain, including the hippocampus, hypothalamus, caudate putamen and nucleus accumbens. Specifically, B(alpha)P increased DA levels in the hippocampus and DA turnover in the caudate putamen. In addition, B(alpha)P suppressed DA levels in the caudate putamen and DA turnover in the nucleus accumbens. B(alpha)P also altered the effect of several dopaminergic agents, L-DOPA, sulpiride and bromocriptine, on DA activity. In particular, B(alpha)P enhanced the L-DOPA-induced increase in the DA turnover ratio in the caudate putamen and increased DA levels in the nucleus accumbens. B(alpha)P also reversed the sulpiride-induced increase of DA turnover in the nucleus accumbens and the bromocriptine-induced increase of DA turnover in the hippocampus. In addition, DA turnover was increased by B(alpha)P in the nucleus accumbens and caudate putamen and DA levels were suppressed in the nucleus accumbens of bromocriptine treated rats, though the drug alone had no effect. These changes indicate that exposure to B(alpha)P and related compounds may affect dopaminergic function in discrete brain regions that are implicated in cognitive functions, psychosis, depression and Parkinson's disease, and may possibly interfere with their pharmacological intervention.     

Consequences of monoamine oxidase inhibition: increased vesicular accumulation of dopamine and norepinephrine and increased metabolism by catechol-O-methyltransferase and phenolsulfotransferase

1. Male Sprague-Dawley rats were injected with saline, L-Dopa or pargyline. 2. Synaptic vesicles were prepared from whole brain homogenates. Catecholamines and their metabolites in brain tissues and in synaptic vesicles were measured by high performance liquid chromatography with electrochemical detection. 3. L-Dopa administration raised brain dopamine markedly but did not significantly change dopamine and norepinephrine in the vesicular fraction. 4. The dopamine increase following L-Dopa was not accompanied by any change in normetanephrine, 3-methoxytyramine or dopamine sulfate. 5. In comparison to the control rats and rats injected with L-Dopa, pargyline-treated rats exhibited significantly higher vesicular norepinephrine and dopamine. 6. The dopamine and norepinephrine increases following pargyline treatment were accompanied by significant increases in 3-methoxytyramine, normetanephrine and dopamine sulfate. 7. The increases in vesicular dopamine and norepinephrine may be the origin of their increased metabolism by extraneuronal enzymes, catechol-O-methyltransferase and phenolsulfotransferase.     

The metabolic rate and vulnerability of dopaminergic neurons,and adenosine dynamics in the cerebral cortex,nucleus accumbens,caudate nucleus,and putamen of the common marmoset

The pathophysiology of the striatum and cerebral cortex were studied from the pharmacological aspect.

Investigation of the dopamine content in the cerebral cortex revealed that the premotor and motor area showed the highest level (61±6.2 ng/g). Intravenous injection of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) at a dose of 10 mg/kg reduced the dopamine content in the caudate nucleus and putamen to 2–3% of the control level in common marmosets, while it fell to 60% in the nucleus accumbens. There was no alteration of the dopamine content in the cerebral cortex. Immunohistochemical staining for tyrosine hydroxylase in the midbrains of MPTP-treated marmosets showed almost complete disappearance of dopaminergic cells from the substantia nigra and good preservation of cells in the ventrotegmental area. Dopaminergic cells projecting to the caudate/putamen, nucleus accumbens, and cerebral cortex showed marked, moderate, and no vulnerability to MPTP, respectively.

After systemic administration of MPTP, dopaminergic neurons projecting to the caudate nucleus and putamen were damaged equally. However, the compensatory increase of dopamine turnover was more prominent in the putamen than in the caudate nucleus. Thus, nigroputaminal dopaminergic neurons may have a higher level of activity than neuron in the caudate. The neural connections and functions of the caudate nucleus and putamen have already been differentiated anatomically or physiologically. This compensatory increase of the dopamine turnover rate is another aspect of functional differences between the caudate nucleus and putamen.

Investigation of the dopamine content in the heat, body, and tail of the caudate nucleus showed no differences in the concentration of dopamine. However, a study of the metabolic rate of dopamine using α-methyl-p-tyrosine, a tyrosine hydoxylase inhibitor, showed higher metabolism of dopamine in the head of the caudate nucleus in common marmosets. Thus, dopaminergic neurons projecting to the caudate nucleus may show topographical differences in their firing rates.

A microdialysis study indicated an increase in the metabolism of adenosine in the striatum of MPTP-treated animals. Cholinergic neurons are interneurons and are one of the main sources of adenosine in the striatum. Dopaminergic input from the substantia nigra acting on cholinergic neurons was decreased following MPTP treatment. The increase of adenosine metabolism suggested that cholinergic neurons in the striatum receive inhibitory inputs from nigrostriatal dopaminergic neurons.