Methylmercury-induced movement and postural disorders in developing rat: regional analysis of brain catecholamines and indoleamines

Subcutaneous administration of methylmercury (MeHg) to rats during early postnatal development resulted in movement and postural disorders by day 22-24. Tissue concentrations of norepinephrine (NE), serotonin (5-HT), dopamine (DA) and selected metabolites were measured in the cerebral cortex, spinal cord and caudate-putamen at the onset of neurological impairment and at two subclinical stages of toxicity. In the cerebral cortex there was a significant increase in tissue concentrations of 5-HT (54-81%) and 5-hydroxyindoleacetic acid (HIAA, 133-178%) at the onset of neurological impairment. Similar increases were detected in the spinal cord for 5-HT (19-43%) and HIAA (98-123%) as well as an increase in the concentration of NE (42-51%). In the caudate-putamen there were significant increases in the concentrations of NE (98-116%), HIAA (108-124%) and DA (28-29%) with a significant decrease in the concentration of 3,4-dihydroxyphenylacetic acid (DOPAC, 20-27%); however, tissue levels of homovanillic acid (HVA) did not change significantly. Many of these changes were detected at subclinical stages of MeHg toxicity. The ratio of HIAA/5-HT, which is frequently used as an estimate of turnover for 5-HT, was significantly increased in all 3 tissues at the onset of neurological impairment (38-94%) and at one subclinical stage (47-114%). The ratio of (DOPAC + HVA)/DA was significantly decreased in caudate-putamen at all 3 stages of toxicity (18-40%). These changes indicate altered metabolism in aromatic amine systems in the developing central nervous system during the pathogenesis of MeHg-induced movement and postural disorder.     

MONOAMINES (SEROTONIN AND CATECHOLAMINES) AND THEIR DERIVATIVES IN INFANTILE AUTISM: AGE-RELATED CHANGES AND DRUG EFFECTS

Levels of dopamine (DA) and its derivatives homovanillic acid (HVA), 3-4 dihydroxyphenylacetic acid (DOPAC), 3-methoxytyramine (3MT) and norepinephrine+epinephrine (NE + E), and serotonin (5HT) and its derivative 5-hydroxyindolacetic acid (5HIAA) were determined from the urine of 156 autistic children aged two to 12 years 6 months, and compared with those of age-matched mentally retarded non-autistic and normal controls. Very significant group and age effects were found for DA, HVA, 3MT, NE + E and 5HT. High HVA, 3MT, NE + E and 5HT levels were found in autistic and non-autistic children. The DA, HVA, 3MT, NE + E, 5HT and 5HIAA levels decreased significantly with age in the three groups. Significantly decreased levels of DA and HVA were observed in autistic children on haloperidol, compared with non-medicated autistic children. The results are discussed in relation to the hypothesis of a maturation defect of monoaminergic systems in autism.     

Influence of time of day on hypothalamic monoaminergic activity in early pregnancy: effect of a previous reproductive experience

Several dopamine-related neurochemical and behavioral responses are influenced by the time of day. The light-dark shift is a major zeitgeber for various functionally important hypothalamic monoaminergic systems. However, these influences are modulated by reproductive state and by reproductive experience (RE) in females. Early pregnancy in rodents generates diurnal and nocturnal prolactin surges that are reduced in intensity in a second pregnancy. Dopamine (DA) is a major inhibitory factor of prolactin synthesis and secretion. Other neurotransmitters such as serotonin (5HT) and norepinephrine (NE) can modulate prolactin secretion as well. Previous works have demonstrated that RE induces changes in central concentrations of both dopamine and serotonin. In addition, RE modulates the responses of both dopaminergic and serotoninergic nerve terminals. The present investigation was designed to examine the possible effects of RE on hypothalamic concentrations of DA, NE, 5HT and their major metabolites homovanillic acid (HVA), 3-4-dihydroxyphenyl acetic acid (DOPAC), 3-methoxy mandelic acid (VMA) and 5-hydroxyindole 3-acetic acid (5HIAA), respectively. These parameters were measured in pregnant rats during the light-dark shift and the prolactin surges. Primi- and multigravid rats were sacrificed on the 7th-8th day of pregnancy between 1700 and 1900 h (light-dark shift and diurnal prolactin surge) or 0200 and 0400 h (nocturnal prolactin surge), and hypothalamic concentrations of DA, NE and 5HT and their metabolites were measured by high performance liquid chromatography coupled to an electrochemical detector (HPLC-ED). Trunk blood was collected and serum prolactin measured by radioimmunoassay. The prolactin surge was confirmed and multigravid rats showed significantly lower serum prolactin levels as compared to primigravid rats between 0200 and 0400 h. During the light-dark shift DA and NE concentrations increased while DOPAC/DA, HVA/DA and 5HIAA/5HT ratios decreased in multigravid rats compared to primigravid rats. Except for 5HIAA/5HT, these differences were not observed during the prolactin nocturnal surge. These results suggest that a previous reproductive experience induces central functional changes during pregnancy which are expressed differently according to the time of day.     

损伤性窒息犬大脑皮质运动区单胺类递质的变化

目的 探讨损伤性窒息犬大脑皮质运动区单胺类递质的变化,为其治疗提供科学依据。方法 建立犬损伤性窒息脑损害模型,用高效液相电化学方法（ＨＰＬＣ－ＤＣ）测定大脑皮质中单胺类递质及其代谢产物在不同时间的改变。结果 大脑皮质运动区在损伤后２小时５－羟吲哚乙酸（５－ＨＩＡＡ）明显升高;８小时后５－羟色胺（５－ＨＴ）、高香草酸（ＨＶＡ）升高;去甲肾上腺素（ＮＥ）及３、４－双羟苯乙酸（ＤＯＰＡＣ）变化不明显。结论 单胺类神经递质参与了损伤性窒息后继发脑损害的病理过程,早期应用５－羟色胺拮抗剂或合成抑制剂是治疗损伤性窒息脑损害的一个可行方法。     

巴曲酶对脑缺血再灌注细胞外液单胺类及其代谢产物的影响——微透析研究

目的巴曲酶对脑缺血再灌流损伤的保护机理。方法采用脑内微透析技术结合高灵敏度的高压液相色谱－电化学检测手段（ＨＰＬＣ－ＥＤ），测定前脑缺血３０ｍｉｎ再灌注１２０ｍｉｎ时的纹状体细胞外液（ＥＣＦ）的ＤＡ、５－ＨＴ和ＮＥ及其代谢产物（５－ＨＩＡＡ）和ＨＶＡ的变化和巴曲酶的影响。结果显示脑缺血时，ＥＣＦＤＡ、ＮＥ及５－ＨＴ明显升高，巴曲酶能显著地降低脑缺血时ＥＣＦＤＡ及再灌注时ＥＣＦＨＶＡ和５－ＨＩＡＡ的水平。结论巴曲酶影响单胺神经递质是对脑缺血再灌注损伤起保护作用的机理之一     

Evidence for acute tolerance to the behavioral effects of lindane: concomitant changes in regional monoamine status.

The effects of the organochlorine insecticide lindane on plus-maze ((+)-maze) behavior of rats and on regional monoamine status were studied at two time points, 30 min and 24 hr post-dosing. Animals were given lindane, 20 mg/kg, 30 min before (L1/2 group), or 40 mg/kg, 24 hr before (L24 group), experimental time; these schedules allowed the study of animals with equivalent brain concentration of lindane at two different time points after administration. The (+)-maze results indicated a reduction in the number of entries into the arms of the maze 30 min after administration of lindane that was not present 24 hr later, suggesting the development of an acute tolerance to the behavioral effects of the chemical. In a parallel group of animals, concentrations of noradrenaline (NA), serotonin (5HT), 5-hydroxyindoleacetic acid (5HIAA), dopamine (DA), dihydroxyphenylacetic acid (DOPAC), and homovanillic acid (HVA) were determined by HPLC in seven brain regions. Significant decreases in NA concentrations were found in L1/2 animals in hippocampus and cerebral cortex and also in the L24 group in the latter region. 5HT/5HIAA ratios increased in several brain regions in the L24 rats but not in the L1/2 rats, thus showing an inverse relationship with behavioral effects. DOPAC/DA and HVA/DA ratios in hypothalamus and cerebral cortex were, by contrast, increased in both groups of treated animals. In conclusion, it appears that an acute tolerance can develop to the behavioral effects of lindane, and that there are modifications produced in central monoaminergic systems by lindane that show brain region and and treatment schedule specificity.(ABSTRACT TRUNCATED AT 250 WORDS)     

帕金森病患者立体定向手术前后脑脊液单胺类递质含量的改变

目的　研究帕金森病 (PD)患者脑立体定向手术前后脑脊液 (CSF)中单胺类递质含量的变化。方法测定 2 6例原发性PD患者 (PD组 )脑立体定向术前、后CSF中多巴胺 (DA)、5 羟色胺 (5 HT)、去甲肾上腺素 (NE)及其代谢产物高香草酸 (HVA)、5 羟吲哚乙酸 (5 HIAA)、3 甲氧基 4羟基苯乙二醇 (MHPG)的含量 ,另外测定 2 5例外科疾病腰麻手术患者 (对照组 )CSF中HVA、5 HIAA、MHPG含量。结果　PD组CSF中HVA、5 HIAA、MHPG含量明显低于对照组 (P <0 0 0 1、P <0 0 5、P <0 0 0 1) ;手术后组的CSF中DA、HVA ,、5 HT、5 HIAA、NE、MHPG含量明显高于手术前组 (其中DA、HVA、5 HT、5 HIAA和NE均P <0 0 0 1;MHPGP <0 0 5 )。结论　PD患者CSF单胺类神经递质代谢产物含量明显降低 ,脑立体定向术可提高PD患者脑部单胺类神经递质及其代谢产物的含量 ,其发生机制可能与DA能神经元的保护作用有关     

Effect of chronic nicotine administration on monoamine and monoamine metabolite concentrations in rat brain

The effects on rat brain tissue monoamine and monoamine metabolite concentrations of chronic nicotine administration at two doses (3 and 12 mg/kg/day) using constant infusion were studied. After 21 days of treatment, tissue concentrations of dopamine (DA), norepinephrine (NE), 5-hydroxytryptamine (5-HT), and several metabolites in striatum, hypothalamus, and frontal cortex were determined by high performance liquid chromatography with electrochemical detection. Compared with a control group, nicotine treatment significantly decreased NE in frontal cortex but not in other regions. The concentration of 5HT also was decreased in frontal cortex but increased in the hypothalamus at the higher dose of nicotine. The 5HT metabolite 5-hydroxyindoleacetic acid (5-HIAA) was not significantly altered in any region. The 5HT index (5-HIAA/5-HT) was significantly decreased in the hypothalamus and increased in frontal cortex at the higher dose. Concentrations of DA and the metabolite homovanillic acid (HVA) were not significantly altered by nicotine. Nevertheless, significant decreases in the DA metabolite dihydroxyphenyl-acetic acid (DOPAC) were observed in both striatum and hypothalamus. Moreover, the DA index [(DOPAC + HVA)/DA] was significantly decreased in all three brain regions. In contrast to other studies using acute dose and in vitro perfusion paradigms that have reported increased CNS catecholamine release stimulated by nicotine, chronic administration appears to be associated with decreased catecholamine turnover in some brain regions.     

Cytomegalovirus infection of the developing brain alters catecholamine and indoleamine metabolism

Tissue concentrations of noradrenaline (NA), serotonin (5-HT), dopamine (DA) and selected metabolites were measured in the spinal cord, cerebellum, cerebral cortex and caudate-putamen of developing mice following intraventricular inoculation with murine cytomegalovirus (MCMV) on postnatal day 10. MCMV-infected animals exhibited transient signs of neurological impairment, including apparent hypertonicity of hindlimb extensors and abnormal gait, beginning on days 14-16 and continuing for 3-5 days. At the onset of neurological impairment, tissue concentrations of NA were significantly reduced in the spinal cord (20%), cerebellum (32%) and cerebral cortex (40%) of infected animals. Levels of 5-HT were significantly increased in the caudate-putamen (50%), while 5-hydroxyindoleacetic acid (5-HIAA) was increased in both the spinal cord (94%) and caudate-putamen (65%). The ratio of 5-HIAA/5-HT, which is frequently used as an estimate of turnover of 5-HT, was significantly increased in the spinal cord (90%) at the onset of neurological impairment. In the caudate-putamen of MCMV-infected animals, there were significant increases in the tissue levels of DA (37%), homovanillic acid (HVA, 41%) and 3,4-dihydroxyphenylacetic acid (DOPAC, 34%). All neurochemical parameters were normal in the MCMV-infected animals by postnatal day 70, approximately 50 days after the resolution of neurological signs. These results indicate transient alterations in monoamine metabolism in the developing nervous system during the pathogenesis of cytomegalovirus-induced movement and postural disorders.     

Effect of neonatal nociceptin or nocistatin imprinting on the brain concentration of biogenic amines and their metabolites

Noradrenaline (NA), dopamine (DA), homovanillic acid (HA), serotonin (5HT) and 5-hydroxyindole acetic acid (5HIAA) content of five brain regions (hypothalamus, hippocampus, brainstem, striatum and frontal cortex) and the cerebrospinal fluid (CSF) was measured in adult (three months old) male and female rats treated neonatally with a single dose of 10 microg nociceptin (NC) or 10 microg nocistatin (NS) for hormonal imprinting. The biogenic amine and metabolite content of cerebrospinal fluid was also determined. In NC treated animals the serotonergic, dopaminergic as well as noradrenergic systems were influenced by the imprinting. The 5HT level increased in hypothalamus, the 5HIAA tissue levels were found increased in hypothalamus. Hippocampus and striatum and the HVA levels increased highly significantly in brainstem. Dopamine level decreased significantly in striatum, however in frontal cortex both noradrenalin and 5HIAA level decreased. Nevertheless, in NS-treated rats decreased NA tissue levels were found in hypothalamus, brainstem and frontal cortex. Decreased DA levels were found in the hypothalamus, brainstem and striatum. NS imprinting resulted in decreased HVA level, but increased one in the brainstem. The 5HT levels decreased in the hypothalamus, brainstem, striatum and frontal cortex, while 5HIAA content of CSF, and frontal cortex decreased, and that of hypothalamus, hippocampus and striatum increased. There was no significant difference between genders except in the 5HT tissue levels of NC treated rats. Data presented show that neonatal imprinting both by NC and NS have long-lasting and brain area specific effects. In earlier experiments endorphin imprinting also influenced the serotonergic system suggesting that during labour release of pain-related substances may durably affect the serotonergic (dopaminergic, adrenergic) system which can impress the animals' later behavior.     

Ischemia in the dorsal hippocampus is associated with acute extracellular release of dopamine and norepinephrine

Summary The cerebral dialysis technique was employed to monitor extracellular concentrations of dopamine (DA), norepinephrine (NE), dihydroxyphenylacetic acid (DOPAC), and homovanillic acid (HVA) in the dorsal hippocampus of gerbils before and after cerebral ischemia induced by carotid artery occlusion. Extracellular concentrations of DA and NE in the dorsal hippocampus increased from baseline levels of <35 fmol/collection interval to 180 and 200 fmol/collection, respectively, within 36 minutes following carotid artery ligation (n=8 animals). Extracellular concentrations of the DA metabolites, DOPAC and HVA, did not change significantly following carotid artery ligation. These data demonstrate that ischemia in the dorsal hippocampus is associated with a mared release of DA and NE. This release may contribute to the selective vulnerability of the dorsal hippocampus to neuronal damage during ischemia.     

Chronic vitamin D deficiency in the weanling rat alters catecholamine metabolism in the cortex

The effect of a vitamin D deficient (--D), vitamin D replete (150 I.U. D3 twice weekly) and normal rat diets for 4 weeks in weanling male rats on the steady-state concentration in several brain sites of dopamine (DA), norepinephrine (NE), and dihydroxyphenylacetic acid (DOPAC) was investigated. The areas of the central nervous system assayed were the brainstem, cerebellum, cerebral cortex, hypothalamus-median eminence, and striatum. The results indicate that DA content of cortex and hypothalamus significantly increased in the --D group compared to the normal diet or D replete groups. The concentrations of DOPAC and NE in the cortex of both --D and D replete rats increased significantly compared to normal diet group. Plasma calcium level was significantly lower in --D group compared to the normal diet or vitamin D replete groups.     

Effect of progesterone on monoamine turnover in the brain of the estrogen-primed rat

The effect of progesterone (P) on monoamine levels and turnover was evaluated in 8 brain nuclei in estrogen-primed rats. Animals were subcutaneously (SC) injected with P or vehicle 21 hours after SC treatment with 5 micrograms of estradiol benzoate (EB). EB-primed animals treated with P showed high levels of lordosis behavior and an LH surge three hours later. Initial concentrations of norepinephrine (NE), dopamine (DA), serotonin (5HT) and 5-hydroxyindole acetic acid were determined in EB-saline treated controls 3 hours after P or vehicle. NE and DA turnover was estimated from the exponential decline of these amines 2 hours after IP injection of alpha-methyl-p-tyrosine (5 hours after P or vehicle). The accumulation of 5HT 20 min following IP injection of pargyline was used as an index of 5HT turnover. P did not affect the initial NE, 5HT or 5HIAA concentrations in any of the brain nuclei studied, but decreased DA content in the arcuate-median eminence region (Ar-ME). The DA rate constant was elevated in the nucleus of the diagonal band of Broca and the DA turnover rate was decreased in the Ar-ME. In the periventricular region (PVE, anterior hypothalamic level) the NE turnover rate (K, pg/microgram protein/hr) and rate constant (k, hr-1) decreased following P treatment. Progesterone treatment decreased the accumulation of 5HT in the ventromedial hypothalamus (VMN, pars lateralis) and the dorsal midbrain central grey (MCG). Progesterone effects on monoamine turnover were not found in the lateral septal, medial preoptic, anterior hypothalamic or dorsal raphe nuclei.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effect of yohimbine on brain monoamines: An in vivo study

Summary Following the administration of yohimbine, an 2-adrenoreceptor antagonist, the levels of norepinephrine (NE), dihydroxyphenylacetic acid (DOPAC), homovanillic acid (HVA), and 5-hydroxyindoleacetic acid (5HIAA) increased significantly in the lateral ventricular fluid of rats. These increases were abolished when animals were pretreated with -methyl-para-tyrosine or reserpine. Dopamine (DA) was not detected in ventricular fluid either before or after yohimbine administration. Yohimbine administration did, however, increase intracellular DA levels in the corpus striatum. These findings indicate that yohimbine promotes NE and DA release in the brain and suggest that it also modifies the activity of the serotonin system.     

BMY-14802 reverses the reduction of striatal dopamine release induced by (+)-3-[3-hydroxyphenyl]-N-(1-propyl)piperidine

Summary Intraperitoneal injection of (+)-3-[3-hydroxyphenyl)-N-(1-propyl)piperidine ((+)-3PPP), a sigma receptor agonist, significantly reduced the striatal levels of dopamine (DA), 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) measured by in vivo microdialysis. These reductions were significantly greater at (+)-3PPP doses of 12 and 24 mg/kg than at 1 mg/ kg. The levels of 5-hydroxyindoleacetic acid (5HIAA) were increased by the injection of (+)-3PPP in dose of 24 mg/kg, but were not affected at lower doses. BMY-14802, a sigma antagonist, alone at doses of 15 mg/kg and 30 mg/kg did not affect the levels of DA, DOPAC, HVA and 5HIAA. Pretreatment with 30 mg/kg BMY-14802 reversed the reduction of the levels of DA induced by 12 mg/kg (+)-3PPP. Although neither 30 mg/kg BMY-14802 nor 12 mg/kg (+)-3PPP affected the levels of striatal 5HIAA, combined treatment with both produced a significant elevation. These findings clearly demonstrate that sigma receptors may regulate DA release from the striatal presynapse.     

Comparative effects of the neurotoxins N-chloroethyl-N-ethyl-2-bromobenzylamine hydrochloride (DSP4) and 6-hydroxydopamine on hypothalamic noradrenergic, dopaminergic and 5-hydroxytryptaminergic neurons in the male rat

The intracerebroventricular (i.c.v.) administration of 6-hydroxydopamine (6-OHDA; 50 micrograms X 3) and the systemic administration of DSP4 (50 mg/kg X 2; i.p.), alone and in combination, were compared for their abilities to alter the concentrations of norepinephrine (NE), dopamine (DA), dihydroxyphenylacetic acid (DOPAC) and 5-hydroxytryptamine (5-HT) in selected hypothalamic and extra-hypothalamic (striatum, frontal cortex, hippocampus) regions of the male rat brain. DSP4 markedly lowered NE concentrations in extrahypothalamic regions, and within the hypothalamus produced a mild and variable reduction of NE without altering concentrations of DA, DOPAC or 5-HT. 6-OHDA markedly lowered NE concentrations in all brain regions, but was without effect on DA, DOPAC and 5-HT concentrations in any region analyzed. Combined treatment with DSP4 and 6-OHDA did not produce additional effects on levels of NE, DA and DOPAC over either drug alone, but did cause a mild reduction of 5-HT in several brain regions. These results indicate that systemic treatments with DSP4 per se are not as effective as i.c.v. 6-OHDA in depleting NE in the hypothalamus, and that when the two neurotoxins are administered there appears to be some destruction of 5-HT neurons.     

Physical and chemical considerations in the in vitro calibration of microdialysis probes for biogenic amine neurotransmitters and metabolites

The object of the present study was to examine the effects of temperature, oxidation, and pH on in vitro relative recovery of catecholamine and indoleamine neurotransmitters and their metabolites using microdialysis probes. Relative recovery of norepinephrine (NE), dihydroxyphenylacetic acid (DOPAC), 5-hydroxyindoleacetic acid (5HIAA), dopamine (DA), homovanillic acid (HVA), and 5-hydroxytryptamine (5HT) increased with temperature from 0 to 46 degrees C. For each compound, the increase in the amount recovered with increasing temperature was different. The stability of norepinephrine and dopamine was not affected at any temperature using deoxygenated calibration standard solutions containing ascorbic acid but was greatly reduced when exposed to ambient air without antioxidant treatment; catecholamine metabolites and the indole compounds were less affected. No change for in vitro relative recovery was observed by varying the pH of the perfusing solution from 6 to 8. Thus, temperature control in probe calibration as well as analyte stability using antioxidant treatment are important in reducing the error when estimating extracellular concentrations of neurotransmitter and metabolites.     

Serotonin, but not dopamine, metabolites are increased in selected brain regions of subordinate male rats in a colony environment.

Subordinate male laboratory rats maintained in mixed-sex groups in a Visible Burrow System habitat show a complex pattern of stress-related changes including enhanced defensive behavior, early mortality and increased voluntary ethanol consumption. Analysis of serotonin (5-HT) and 5-hydroxyindoleacetic acid (5-HIAA) levels indicated that 5-HT levels do not differ between colony subordinates, colony dominants, and singly-housed control animals. However, 5-HIAA levels were higher in subordinates than either dominants or control animals in the preoptic area, amygdala, hippocampus, and spinal cord, and, were higher than dominants only, in entorhinal cortex. Subordinates' regional 5-HIAA/5-HT ratios were reliably higher than those of dominant or control animals in midbrain and spinal cord and reliably higher than dominants only, in hypothalamus. Dopamine (DA) and dihydroxyphenylacetic acid (DOPAC) levels and DA/DOPAC ratios were affected neither in hypothalamus nor midbrain. These findings suggest that a consistent increase of 5-HIAA levels in selected brain regions of subordinate rats may represent a biological substrate for a well-characterized pattern of alterations in defensive behaviors for these animals.     

Aggression in humans correlates with cerebrospinal fluid amine metabolites.

Cerebrospinal fluid of the major central metabolites of serotonin (5HT), norepinephrine (NE), and dopamine (DA)--5-hydroxyindoleacetic acid (5HIAA), 3-methoxy-4-hydroxy=phenylglycol (MHPG), and homovanillic acid (HVA), respectively--were studied in a group of 26 age-similar military men with no history of major psychiatric illness, but with various personality disorders and difficulties adjusting to military life. Independently scored history of aggressive behavior showed a significant negative correlation with 5HIAA (r = -0.78) and a significant positive correlation with MHPG (r = 0.64).     

Striatal L-dopa metabolism studied in vivo in rats with nigrostriatal lesions

Summary We have used cerebral dialysis to monitor striatal metabolism of exogenously administered L-dopa (L-dihydroxyphenylalanine) in rats with unilateral lesions of the substantia nigra. The concentration of extracellular dopamine (DA) increased in both striata following L-dopa administration but the increase was markedly attenuated in the lesioned striatum. The formation of dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA), the major DA metabolites, was also reduced in the lesioned striata following L-dopa administration; however, the reduction was not as great as was that of DA formation. A significant metabolism of exogenous L-dopa to 3-O-methyldopa occurred in both striata. L-dopa administration transiently increased extracellular levels of 5-hydroxyindoleacetic acid (5 HIAA) in both the lesioned and intract striata.These results suggest that the striatum with a reduction in DA nerve terminals is deficient both in the capacity to synthesize DA and in the storage mechanisms necessary to protect the newly synthesized DA from oxidative metabolism.