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Parkinson's disease (PD) is diagnosed by the onset of motor symptoms and treated long after its onset. Therefore, the development of the early diagnosis of PD is a priority for neurology. Advanced methodologies for this include (1) searching for patients at risk of developing prodromal PD based on premotor symptoms; (2) searching for changes in the body fluids in these patients as diagnostic biomarkers; (3) verifying the diagnosis of prodromal PD and diagnostic-value biomarkers using positron emission tomography (PET); (4) anticipating the development of motor symptoms. According to our data, the majority of patients (n = 14) at risk of developing PD selected in our previous study show pronounced interhemispheric asymmetry in the incorporation of 18F-DOPA into dopamine synthesis in the striatum. This was assessed for the caudate nucleus and putamen separately using the specific binding coefficient, asymmetry index, and putamen/caudate nucleus ratio. Interhemispheric asymmetry in the incorporation of 18F-DOPA into the striatum provides strong evidence for its dopaminergic denervation and the diagnostic value of previously identified blood biomarkers. Of the 17 patients at risk of developing prodromal PD studied using PET, 3 patients developed motor symptoms within a year. Thus, our study shows the promise of using the described methodology for the development of early diagnosis of PD. [ABSTRACT FROM AUTHOR]

[Display omitted] • Co-administration of rotenone and manganese decreases body weight. • Manganese enhances the neurotoxicity of rotenone in the striatum. • Absence of mitochondrial complex I inhibition after rotenone or manganese treatment. Parkinson's disease (PD) is a complex disorder, primarily of idiopathic origin, with environmental stressors like rotenone and manganese linked to its development. This study explores their potential interaction and resulting neurotoxicity, aiming to understand how environmental factors contribute to PD. In an eight-day experiment, male Wistar rats weighing 280–300 g were subjected to rotenone, manganese, or a combination of both. Various parameters were assessed, including body weight, behavior, serum markers, tissue damage, protein levels (tyrosine hydroxylase, Dopamine- and cAMP-regulated neuronal phosphoprotein –DARPP-32-, and α-synuclein), and mitochondrial function. Manganese heightened rotenone's impact on reducing food intake without causing kidney or liver dysfunction. However, the combined exposure intensified neurotoxicity, which was evident in augmented broken nuclei and decreased tyrosine hydroxylase and DARPP-32 levels in the striatum. While overall mitochondrial function was preserved, co-administration reduced complex IV activity in the midbrain and liver. In conclusion, our findings revealed a parallel toxic effect induced by rotenone and manganese. Notably, while these substances do not target the same dopaminergic regions, a notable escalation in toxicity is evident in the striatum, the brain region where their toxic effects converge. This study highlights the need for further exploration regarding the interaction of environmental factors and their possible impact on the etiology of PD. [ABSTRACT FROM AUTHOR]

Inherited autosomal recessive mutations of the manganese (Mn) transporter gene SLC39A14 in humans, results in elevated blood and brain Mn concentrations and childhood-onset dystonia-parkinsonism. The pathophysiology of this disease is unknown, but the nigrostriatal dopaminergic system of the basal ganglia has been implicated. Here, we describe pathophysiological studies in Slc39a14-knockout (KO) mice as a preclinical model of dystonia-parkinsonism in SLC39A14 mutation carriers. Blood and brain metal concentrations in Slc39a14-KO mice exhibited a pattern similar to the human disease with highly elevated Mn concentrations. We observed an early-onset backward-walking behavior at postnatal day (PN) 21 which was also noted in PN60 Slc39a14-KO mice as well as dystonia-like movements. Locomotor activity and motor coordination were also impaired in Slc39a14-KO relative to wildtype (WT) mice. From a neurochemical perspective, striatal dopamine (DA) and metabolite concentrations and their ratio in Slc39a14-KO mice did not differ from WT. Striatal tyrosine hydroxylase (TH) immunohistochemistry did not change in Slc39a14-KO mice relative to WT. Unbiased stereological cell quantification of TH-positive and Nissl-stained estimated neuron number, neuron density, and soma volume in the substantia nigra pars compacta (SNc) was the same in Slc39a14-KO mice as in WT. However, we measured a marked inhibition (85–90%) of potassium-stimulated DA release in the striatum of Slc39a14-KO mice relative to WT. Our findings indicate that the dystonia-parkinsonism observed in this genetic animal model of the human disease is associated with a dysfunctional but structurally intact nigrostriatal dopaminergic system. The presynaptic deficit in DA release is unlikely to explain the totality of the behavioral phenotype and points to the involvement of other neuronal systems and brain regions in the pathophysiology of the disease.

Background: Asymmetric hemispheric loss of dopaminergic neurons is one of the characteristic features of Parkinson's disease (PD). However, it is still debated if right or left asymmetry differently affects cognitive and motor progression. Objectives: The objective of this study was to investigate, for the first time, the relevance of dopamine transporter (DAT) asymmetry on cognitive and motor manifestations at onset and at 4‐year progression in drug‐naïve PD. Methods: From the Parkinson's Progression Markers Initiative multicenter cohort, we identified 249 right‐handed patients with PD with baseline asymmetry greater than 20% in putamen DAT binding at single‐photon emission computed tomography. A predominant putamen asymmetry was found on the left in 143 patients (PD‐left), and on the right side in 106 patients (PD‐right); we compared them with 196 healthy controls. Patients were followed longitudinally (2‐year and 4‐year visits), examining their clinical, cognitive, and imaging data. Results: At baseline, the PD‐left group showed worse performance on the Symbol Digit Modality Test, an attention and processing‐speed test, and lower cerebrospinal fluid β‐amyloid levels than the PD‐right group. These differences were maintained at follow‐up, declining over time in both groups. By contrast, the PD‐right group showed greater motor impairment at baseline, which increased over 4 years. Striatal DAT binding decreased over time in both groups, but the PD‐right group showed a steeper decline, particularly during the first 2‐year follow‐up. Putaminal asymmetry assessed at baseline was maintained over time. Conclusions: These findings suggest that hemispheric asymmetric dopaminergic denervation influences PD cognitive and motor performance as well as progression. Predominant right hemisphere nigrostriatal dopaminergic loss is associated with greater motor severity, whereas more pronounced left hemisphere denervation affects cognitive manifestations at onset and their progression. © 2021 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society [ABSTRACT FROM AUTHOR]

• WAG/Rij rats with genuine spike-wave discharges were classified as 'epileptic'. • Absence of SWDs in 'non-epileptic' rats did not relate to changes in SNc. • Rudimentary SWDs were found in 'epileptic' and 'non-epileptic' subjects. • Rudimentary SWDs were longer in subjects with less neurons in SNc. • Low number of neurons in SNc was linked to severe epilepsy and sleep disturbance. Spike-wave discharges (SWDs) are EEG hallmarks of absence epilepsy, and they spontaneously appear in adult WAG/Rij rats. SWDs are known to be vigilance-dependent and are modulated by monoaminergic mechanisms. It is also known that loss of neurons in the center of the nigrostriatal dopamine system, substantia nigra pars compacta (SNc), is associated with a variety of sleep disorders. We hypothesized that a disorder of the nigrostriatal dopamine system described for WAG/Rij rats might facilitate generation of SWDs through changes in vigilance state and the quality of sleep. Our study was conducted in 'epileptic' and 'non-epileptic' phenotype (less than 1 SWDs per h). Analysis included (1) EEG examination, i.e., analysis of SWDs, rudimentary SWDs and slow wave sleep EEG and (2) microstructural examination of SNc, i.e., measuring its size and the number of neurons and glial cells. No differences in size and cellular content of SNc were found between 'epileptic' and 'non-epileptic' phenotypes. Meanwhile in 'epileptic' subjects, the number of SWDs correlated with the number of neurons in SNc (SWDs more frequently occurred in subjects with fewer neurons in SNc). Rudimentary SWDs were found in both phenotypes. No differences in number and duration of rudimentary SWDs were found between 'epileptic' and 'non-epileptic' phenotypes. Spike-wave EEG activity showed strong association with the number of neurons in SNc: subjects with fewer neurons in SNc were characterized by higher number of SWDs and longer rudimentary SWDs. In sum, our data suggested that intense epileptic EEG activity (in the form of SWDs and rudimentary SWDs) might lead to sleep disruption. However, the lack of direct correlations between sleep parameters and SWDs number indicated that the link between sleep features, SNc cellularity and spike-wave EEG activity could be more complex than we had expected. [ABSTRACT FROM AUTHOR]

[Display omitted] • Toxicokinetics and toxicodynamics of diphenylarsinic acid (DPAA) were investigated. • Microdialysis was applied to free-moving mice given a single oral administration. • Concentration-time profiles for DPAA in blood and striatum dialysates were obtained. • Rapid absorption into the blood and the BBB penetrability of DPAA was suggested. • DPAA administration affected the extracellular dopamine level in the mouse striatum. Diphenylarsinic acid (DPAA), an artificial phenyl arsenic compound, is considered a groundwater pollutant in Japan. Previous human and animal studies suggested that DPAA affects the central nervous system; however, these effects are poorly understood. The present study investigated the toxicokinetic characteristics and effects of DPAA on dopamine (DA) in the striatum of free-moving mice after a single oral administration. In a simultaneous blood and brain microdialysis study, only DPAA was detectable in both blood and striatum dialysate samples immediately after DPAA administration. DPAA concentrations in the striatum and blood dialysate rapidly reached a maximum, then decreased over time in an essentially parallel manner. A more detailed brain microdialysis examination of intracerebral kinetics revealed that the concentration of DPAA in the striatum dialysate began to increase within 15 min, reaching a maximum approximately 1 h after administration, and then decreased with a biological half-life of approximately 2 h. Moreover, a single oral administration of DPAA at 0.5-32 mg/kg affected the extracellular DA level in the striatum. The effect on DA level changed slowly after DPAA administration, with a bell-shaped dose-response relationship. The present study suggests that DPAA is rapidly absorbed into the blood circulating in the gastrointestinal tract and passes through the blood-brain barrier to subsequently affect DA levels in the striatum in mice after a single oral administration. [ABSTRACT FROM AUTHOR]

Objective: In right-handed patients with Parkinson's disease (PD) or isolated rapid eye movement sleep behavior disorder, dopamine transporter (DAT) [(123)I]β-carboxymethyoxy-3-β-(4-iodophenyl) tropane single photon emission computed tomography (SPECT) shows predominant nigrostriatal deficit in the left striatum. This suggests that in PD patients, the nigrostriatal system of the dominant hemisphere is more susceptible to disease-related dysfunction. To confirm this hypothesis, we investigated whether the nigrostriatal function is symmetric in healthy controls and in patients with PD.Methods: In 113 right-handed healthy controls and 279 right-handed early-PD patients, we examined the striatal dopaminergic terminals function in each hemisphere using DAT-SPECT.Results: In the controls, DAT-SPECT showed symmetric specific binding ratios in the putamen and caudate nucleus of each hemisphere. In patients with PD, the specific binding ratio was lower in the left than in the right putamen.Conclusions: Right-handed healthy controls have symmetric nigrostriatal dopaminergic function. The left hemispheric predominance of nigrostriatal deficit seen in right-handed premotor and manifest PD represents an early pathological feature of the disease. © 2020 International Parkinson and Movement Disorder Society. [ABSTRACT FROM AUTHOR]

Parkinson's disease (PD) and Alzheimer's disease exhibit common features of neurodegenerative diseases and can be caused by numerous factors. A common feature of these diseases is neurotoxic inflammation by activated microglia, indicating that regulation of microglial activation is a potential mechanism for preserving neurons in the adult brain. Recently, we reported that upregulation of prothrombin kringle-2 (pKr-2), one of the domains that make up prothrombin and which is cleaved and generated by active thrombin, induces nigral dopaminergic (DA) neuronal death through neurotoxic microglial activation in the adult brain. In this study, we show that silibinin, a flavonoid found in milk thistle, can suppress the production of inducible nitric oxide synthase and neurotoxic inflammatory cytokines, such as interleukin-1β and tumor necrosis factor-α, after pKr-2 treatment by downregulating the extracellular signal-regulated kinase signaling pathway in the mouse substantia nigra. Moreover, as demonstrated by immunohistochemical staining, measurements of the dopamine and metabolite levels, and open-field behavioral tests, silibinin treatment protected the nigrostriatal DA system resulting from the occurrence of pKr-2-triggered neurotoxic inflammation in vivo. Thus, we conclude that silibinin may be beneficial as a natural compound with anti-inflammatory effects against pKr-2-triggered neurotoxicity to protect the nigrostriatal DA pathway and its properties, and thus, may be applicable for PD therapy. [ABSTRACT FROM AUTHOR]

There is a controversy over the effects of testosterone supplements on dopaminergic function. Both neuroprotective and toxic effects of testosterone supplements are reported. The status of oxidative stress seems to explain the neuroprotective or toxic properties of testosterone. To determine the efficacy of testosterone supplements in different status of oxidative stress, the present studies analyzed the dopamine (DA)-related behaviors and neurochemical indices, as well as markers of nigrostriatal dopaminergic (NSDA) system in reserpine-treated aged male rats followed by testosterone propionate (TP) supplements. The status of oxidative stress of experimental animals was evaluated by analyzing oxidative stress parameters and nuclear factor erythroid 2-related factor 2 (Nrf2)-antioxidant response element (ARE) signaling pathway in substantia nigra (SN). Consistent with our previous studies, TP supplements to 21-month old aged male rats had the beneficial effects on NSDA system and DA-related behaviors and enhanced the antioxidative capabilities in SN. However, the beneficial effects of TP supplements on NSDA system and DA-related behaviors in aged male rats were reversed by reserpine pretreatment to them. Reserpine treatment induced the severe oxidative stress and reduced the expressions of Nrf2, heme oxygenase-1 (HO-1) and NAD(P)H:quinone oxidoreductase-1 (NQO1) in the SN of aged male rats. The TP supplements to reserpine-pretreated aged male rats exacerbated the defects in NSDA system and DA-related behaviors, aggravated oxidative damages and downregulated the expression of Nrf2, HO-1 and NQO1 in the SN. These results suggested that the efficacy of TP supplements on impaired NSDA system was related to the status of oxidative stress in experimental rats.

Dysfunction of the N-methyl-D-aspartate (NMDA) receptor has been implicated in the pathogenesis of schizophrenia. Although agonists for the glycine-binding sites of NMDA receptors have potential as new medication for schizophrenia, their modulation of antipsychotic-induced extrapyramidal side effects (EPS) has not yet been clarified. We herein evaluated the effects of glycine-binding site stimulants of NMDA receptors on antipsychotic-induced EPS in mice and rats. D-cycloserine (DCS) and D-serine significantly improved haloperidol (HAL)-induced bradykinesia in mice, whereas glycine showed no effects. Sodium benzoate, a D-amino acid oxidase inhibitor, also attenuated HAL-induced bradykinesia. Improvements in HAL-induced bradykinesia by DCS were antagonized by the NMDA antagonist dizocilpine or nitric oxide synthase inhibitor L-NG-Nitro-L-arginine methyl ester. In addition, DCS significantly reduced HAL-induced Fos expression in the dorsolateral striatum without affecting that in the nucleus accumbens. Furthermore, a microinjection of DCS into the substantia nigra pars compacta significantly inhibited HAL-induced EPS concomitant with elevations in dopamine release in the striatum. The present results demonstrated for the first time that stimulating the glycine-binding sites of NMDA receptors alleviates antipsychotic-induced EPS by activating the nigrostriatal dopaminergic pathway, suggesting that glycine-binding site stimulants are beneficial not only for efficacy, but also for side-effect management. [ABSTRACT FROM AUTHOR]

The effects of testosterone propionate (TP) supplements on the coordinated motor behavior and nigrostriatal dopaminergic (NSDA) system were analyzed in aged male rats. The present study showed the coordinated motor behavioral deficits, the reduced activity of NSDA system and the decreased expression of vesicular monoamine transporter 2 (VMAT2) in 24 month-old male rats. Long term TP treatment improved the motor coordination dysfunction with aging. Increased tyrosine hydroxylase and dopamine transporter, as well as dopamine and its metabolites were found in the NSDA system of TP-treated 24 month-old male rats, indicative of the amelioratory effects of TP supplements on NSDA system of aged male rats. The enhancement of dopaminergic (DAergic) activity of NSDA system by TP supplements might underlie the amelioration of the coordinated motor dysfunction in aged male rats. TP supplements up-regulated VMAT2 expression in NSDA system of aged male rats. Up-regulation of VMAT2 expression in aged male rats following chronic TP treatment might be involved in the maintenance of DAergic function of NSDA system in aged male rats. [ABSTRACT FROM AUTHOR]

The potential influence of intranasal testosterone propionate (InTP) supplements on mesodopaminergic system in aged male rats was investigated by analyzing the exploratory and motor behaviors as well as dopamine neurobiochemical indices. Meanwhile, oxidative stress parameters and pathway of nuclear factor erythroid 2-related factor 2 (Nrf2)-binding antioxidant response elements (Nrf2-ARE) were examined to check whether the Nrf2-ARE pathway was involved in the InTP-induced alteration of mesodopaminergic system in aged male rats. The exploratory and motor behavioral deficits, as well as the reduced expression of dopamine, tyrosine hydroxylase, and dopamine transporter, which indicated the declined activity of mesodopaminergic system, were ameliorated in rats administered with 12-week InTP. The results indicated that chronic InTP supplements could effectively influence the brain function activity in a way opposite to the effect of aging on the mesodopaminergic system of rats. The increased levels of Nrf2, heme oxygenase-1, and NAD(P)H:quinone oxidoreductase-1 in the substantia nigra and ventral tegmental area, but not in the hippocampus of InTP-administered aged male rats, indicated that the ameliorative effect of InTP supplements on mesodopaminergic system might be related to the region-specific activation of the Nrf2-ARE pathway. [ABSTRACT FROM AUTHOR]

The article focuses on a study that compares FP-CIT PET which detects the differences in regional dopamine transporter (DAT) density in the brain in subtypes of early Parkinson's disease (PD). It mentions that there are differences in nigrostriatal dopaminergic dysfunction between the two PD subtypes is unknown.

Parkinson's disease (PD), one of the most frequent neurodegenerative disorders, is a progressive multi-organ proteinopathy caused by misfolded α-synuclein (αSyn) with variegated motor and nonmotor deficits owing to a spreading process of synaptic and neuronal loss in the nervous system. The motor core deficits of PD including rigidity, akinesia, rest tremor, and postural instability are attributed to the loss of dopaminergic nigrostriatal system, while the nonmotor alterations, such as hyposmia, autonomic and other dysfunctions frequently antedating motor symptoms are linked to widespread distribution of αSyn in the central, autonomic and peripheral nervous system and multiple organs. Recent studies have shown that αSyn aggregation in presynaptic terminals that predates the formation of Lewy bodies (LB), the characteristic markers of PD, is a key event in the pathogenesis of PD and other synucleinopathies. Progress in our understanding of the underlying mechanisms include insights into the functional organization of the basal ganglia and related cortico-subcortical circuits and their relations with morphological and pathophysiological lesions in the nervous system. The pathomechanisms underlying the cardinal motor abnormalities and nonmotor manifestations are briefly reviewed. [ABSTRACT FROM AUTHOR]

Over the last decade, several clinical reports have outlined cases of early-onset manganese (Mn)-induced dystonia-parkinsonism, resulting from loss of function mutations of the Mn transporter gene SLC39A14. Previously, we have performed characterization of the behavioral, neurochemical, and neuropathological changes in 60-day old (PN60) Slc39a14-knockout (KO) murine model of the human disease. Here, we extend our studies to aging Slc39a14-KO mice to assess the progression of the disease. Our results indicate that 365-day old (PN365) Slc39a14-KO mice present with markedly elevated blood and brain Mn levels, similar to those found in the PN60 mice and representative of the human cases of the disease. Furthermore, aging Slc39a14-KO mice consistently manifest a hypoactive and dystonic behavioral deficits, similar to the PN60 animals, suggesting that the behavioral changes are established early in life without further age-associated deterioration. Neurochemical, neuropathological, and functional assessment of the dopaminergic system of the basal ganglia revealed absence of neurodegenerative changes of dopamine (DA) neurons in the substantia nigra pars compacta (SNc), with no changes in DA or metabolite concentrations in the striatum of Slc39a14-KO mice relative to wildtype (WT). Similar to the PN60 animals, aging Slc39a14-KO mice expressed a marked inhibition of potassium-stimulated DA release in the striatum. Together our findings indicate that the pathophysiological changes observed in the basal ganglia of aging Slc39a14-KO animals are similar to those at PN60 and aging does not have a significant effect on these parameters., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Published by Elsevier B.V.)

Abstract: Testosterone has been shown to affect motor behavior and nigrostriatal dopaminergic (NSDA) system in young and adult male rats. However, it is not known whether exogenous testosterone intervention to aged male rats can ameliorate age-related motor impairment. Thus, in the present study, the open field motor behavior and adhesive tape removal motor performance as well as the expression of tyrosine hydroxylase (TH) and dopamine transporter (DAT) of NSDA system were examined in aged male rats following chronic subcutaneous injections of testosterone propionate (TP). Aged rats showed significantly reduced open field motor behavior and adhesive tape removal motor performance compared to adult rats. Chronic TP supplement significantly ameliorated the age-related motor deficits. The expression of TH and DAT of NSDA system was significantly enhanced in TP-treated aged rats revealed by RT-PCR, Western blot and immunohistochemistry analysis respectively. The results imply that chronic TP treatment may favorably improve the declined motor behavior and motor performance with aging. Testosterone propionate supplement that facilitated NSDA system may influence the maintenance of motor behavior and performance in aged rats. [Copyright &y& Elsevier]

In this paper, we propose an automatic system for quantitative measurements of basal ganglia activity by 3-D striatum activity reconstruction from ^123I FP-CIT SPECT images for investigations on the nigrostriatal dopaminergic system. In detail, the proposed system consists of three main parts: 1) Image Enhancement, carried out by means of Active Contours Models, 2) 2-D Striatum segmentation in the HSV color space, and 3) Surface Rendering by an extended marching cubes algorithm where the isovalue of the striatum's isosurface and the final 3-D volume are automatically computed. The validation of the model was done on the anthropomorphic Alderson RSD phantom, achieving encouraging results both in terms of striatum activity measurement (average error of 1.57% \pm 1.28%) and in terms of volume measurements (average error of 0.77% \pm 1.42%). Finally, an evaluation on 128 patients was carried out, suggesting novel ranges (to be further clinically validated) of the reference values for striatum activity that may be employed for the differential diagnosis of Parkinson, Vascular Parkinsonism, Alzheimer, and Essential Tremor. [ABSTRACT FROM PUBLISHER]

Abstract: The substantia nigra (SN) is known to be involved in the memorization of several conditioned responses. To investigate the role of the SN in fear conditioning consolidation this neural site was subjected to fully reversible tetrodotoxin (TTX) inactivation during consolidation in adult male Wistar rats which had undergone fear training to acoustic CS and context. TTX was stereotaxically administered to different groups of rats at increasing intervals after the acquisition session. Memory was assessed as conditioned freezing duration measured during retention testing, always performed 72 and 96h after TTX administration. In this way there was no interference with normal SN function during either acquisition or retrieval phases, so that any amnesic effect could be due only to consolidation disruption. The results show that SN functional integrity is necessary for contextual fear response consolidation up to the 24-h after-acquisition delay. On the contrary SN functional integrity was shown not to be necessary for the consolidation of acoustic CS fear responses. The present findings help to elucidate the role of the SN in memory consolidation and better define the neural circuits involved in fear memories. [Copyright &y& Elsevier]

Tardive dyskinesia, the most serious iatrogenic movement disorder, has been tentatively associated with nigrostriatal dopaminergic supersensitivity and with oxidative stress. It is also suggested that long-term neuroleptic treatment does not cause oral dyskinesia (OD), but interacts with some substrate of brain aging, resulting in the premature emergence of OD, that can occur spontaneously with aging. In order to investigate a possible role of nigrostriatal dopaminergic supersensitivity and of oxidative stress in aging- and reserpine-induced OD, the stereotyped behavior induced by dopaminergic agonists, a functional index of dopaminergic striatal activity, as well as the striatal antioxidant enzymes glutathione peroxidase and catalase were assessed. We demonstrate that, opposite to normotensive Wistar rats (NWR), spontaneously hypertensive rats (SHR) do not develop aging- or reserpine-OD. There were no differences between NWR and SHR in stereotyped behavior or in striatal glutathione peroxidase activity. Adult and old SHR presented higher striatal catalase activity relative to NWR, and aging increased it only in SHR. The catalase inhibitor aminotriazole reverted the absence of aging- and reserpine-induced OD in SHR. Our results suggest an important role of striatal catalase in the development of reserpine- and aging-induced OD. [Copyright &y& Elsevier]

The effects on striatal high affinity glutamate uptake (HAGU) of an apomorphine injection administered either alone or along with an electrical stimulation of the frontal cortex were compared between intact control rats and animals with 6-hydroxydopamine (6-OHDA) induced lesions of the nigrostriatal dopaminergic neurons. 6-OHDA injury was previously shown to have no effect either on basal HAGU or on the HAGU increase occurring in response to cortical stimulation. Apomorphine injected 1 h before HAGU determination at a dose of 5 mg/kg did not modify basal HAGU but totally abolished HAGU responsiveness to cortical stimulation applied 30 min after the apomorphine administration in both groups of animals. However, the duration of apomorphine induced inhibition of the cortically evoked striatal HAGU response in animals with 6-OHDA injury greatly exceeded that observed in intact rats. Indeed, in intact animals, cortical stimulation again became able to increase striatal HAGU when applied more than 6 h after apomorphine injection, while in 6-OHDA injected rats, HAGU responsiveness to cortical stimulation was restored only as from 7 days after apomorphine administration. Moreover, in rats given 6-OHDA injections apomorphine efficiently inhibited the activating effect of cortical stimulation on HAGU at doses at least 20 times lower than those required to obtain the same effect in intact animals. These results suggest that in both intact and 6-OHDA injected rats, apomorphine acts by counteracting the HAGU increase occurring in response to cortical stimulation and that the sites involved in this action develop a supersensitivity response to striatal dopaminergic deafferentation. Taken as a whole, these data reinforce our previous suggestion that the nigrostriatal dopaminergic pathway may be physiologically able to exert a neuromodulatory action on striatal HAGU, counteracting the HAGU activation induced by an increase in corticostriatal neuron discharge. [ABSTRACT FROM AUTHOR]