Dopamine-sensitive adenylate cyclase and TH-SCH 23390 binding parameters were measured in the rat substantia nigra and striatum 15 days after the injection of 6-hydroxydopamine into the medial forebrain bundle. The activity of nigral dopamine-sensitive adenylate cyclase and the binding of TH-SCH 23390 to rat nigral ...

Parkinson's disease is characterized by the depletion of glutathione (GSH) in, the substantia nigra and the degeneration of nigral dopamine neurons. In our study we examined the relationship between cellular GSH depletion and neuronal degeneration. Using ...

factors, antioxidants and anti-apoptotic agents. When neural grafts are transplanted into the brain the survival of transplanted dopamine neurons in rat brains. EXPERIMENTAL PROCEDURES Experimental design of transplanted dopamine neurons in rat brains by twofold. The peptide is also found to signi�cantly reduce

1. Clinical and experimental studies support the view that nigrostriatal dopaminergic neurons are involved in the maintenance of muscle tone. 2. The effects of inactivating dopamine receptors in the rat substantia nigra on muscle tone, assessed as tonic electromyographic (EMG) activity, was investigated. 3. Dopamine receptors were inactivated by injections ...

Nociceptin/orphanin FQ (N/OFQ) peptide (NOP) receptor antagonists proved to be effective in alleviating experimental parkinsonism. Nonetheless, loss of effectiveness or even worsening of parkinsonian symptoms have been observed at high doses. With the aim of clarifying the circuitry underlying the dual action of NOP receptor antagonists and the role of endogenous dopamine, the ...

The dopamine transporter is the primary means of inactivating synaptic dopamine as well as a major site of action for psychostimulants (such as cocaine and amphetamine) and for neurotoxins that induce parkinsonism. In the present study, a human dopamine transporter partial cDNA clone obtained by polymerase chain reaction exhibited 87% ...

Objective: Oxidative stress is a hallmark in the pathogenesis of Parkinson disease (PD), which involves the selective loss of nigral dopaminergic neurons in PD. Resveratrol (3,5,4'-trihydroxy-trans-stilbene) is well known for its powerful antioxidant property and a wide range of other biological effects. In this study, we investigated the protective effect of resveratrol ...

Despite the presence of Zn(2+) in high levels in Parkinson brain, it is not yet clearly answered whether and how Zn(2+) alters the electrical activity of neurons in substantia nigra (SN). Here we show that Zn(2+) alters the intrinsic activity of nigral dopamine neurons in dual ways, that is, excitation or inhibition, by modulating the gating properties of ...

Recessively inherited loss-of-function mutations in the parkin, DJ-1, or PINK1 gene are linked to familial cases of early-onset Parkinson's diseases (PD), and heterozygous mutations are associated with increased incidence of late-onset PD. We previously reported that single knockout mice lacking Parkin, DJ-1, or PINK1 exhibited no nigral degeneration, even though evoked ...

The powerful trophic effects that glial cell line-derived neurotrophic factor (GDNF) exerts on midbrain dopamine neurones suggest its use in treating Parkinson's disease. However, some important questions remain about the possible therapeutic applications of GDNF. Here we demonstrate that the chronic infusion of 5 or 15 micro g/day GDNF into the lateral ventricle or the ...

The effect of medial forebrain bundle (MFB) stimulation on neostriatal dopamine levels was examined using in vivo microdialysis in urethane-anesthetized and awake, freely-moving rats in conjunction with single unit extracellular recordings from antidromically identified nigral dopaminergic neurons. Dialysis samples were collected during baseline periods or ...

Single photon emission computed tomography (SPECT) using [(123)I]FP-CIT as radioligand for the dopamine transporter has become a widely used tool to monitor the integrity of the nigrostriatal dopaminergic projection in Parkinson's disease (PD). Previous studies with pinhole SPECT in small animals have demonstrated that the striatal [(123)I]FP-CIT binding indeed correlates with ...

Peroxisome proliferator-activated receptor alpha (PPAR-?), which is expressed by neurons of the nigrostriatal circuit, plays a prominent role in oxidative stress and neuroinflammation. The objectives were: (i) to discern if levels of antioxidant molecules and pro-inflammatory cytokines, along with PPAR-? expression are modified in the nigrostriatal region of null PPAR-? mice, (ii) to discern ...

Parkinson's disease (PD) is characterized by progressive death of dopamine (DA) neurons in the substantia nigra pars compacta. We report a rat model that exhibits progressive death of nigral neurons following unilateral injection of kainic acid in the striatum. In situ end-labeling revealed significant numbers of dying nigral neurons ...

Methods for the assessment of akinesia in the unilateral rat Parkinson model have so far been lacking. The experiments reported here evaluate the usefulness of a new "stepping test" to monitor forelimb akinesia in rats with unilateral 6-hydroxydopamine (6-OHDA) lesions of the mesencephalic dopamine (DA) system, and to assess the ability of DA-receptor agonists and fetal DA ...

Methamphetamine (mAMPH) is an addictive psychostimulant drug that releases monoamines through nonexocytotic mechanisms. In animals, binge mAMPH dosing regimens deplete markers for monoamine nerve terminals, for example, dopamine and serotonin transporters (DAT and SERT), in striatum and cerebral cortex. Although the precise mechanism of mAMPH-induced damage to monoaminergic ...

In order to explore the neurophysiology of nicotine withdrawal, we examined the activity of substantia nigra (A9) and ventral tegmental area (A10) dopamine cells in rats undergoing withdrawal from chronic exposure to nicotine. Animals were exposed to nicotine (6 mg kg-1 day-1 base) via s.c. implanted osmotic minipumps. After 12 days ...

This study examined the effects of the novel atypical antipsychotic olanzapine (LY170053) on the activity of substantia nigra pars compacta (A9) and ventral tegmental area (A10) dopamine cells in anesthetized rats. Acute administration of olanzapine (10, 20 mg/kg sc) increased the number of spontaneously active A10, but not A9, ...

Extracellular single-unit activities of dopamine neurons were recorded using chloral hydrate anaesthetized rats. We examined the reversal effects of the selective dopamine D4 receptor blockers, NRA0160 (2-Carbamoyl-4-(4-fluorophenyl)-5-[2-[4-(3-fluorobenzylidene) piperidin-1-yl] ethyl] thiazole) and L-745,870 (3-[[4-(4-chlorophenyl) piperazin-1-yl] ...

Deep brain stimulation of the subthalamic nucleus (STN-DBS) is efficacious in treating the motor symptoms of Parkinson�s disease (PD). However, the impact of STN-DBS on the progression of PD is unknown. Previous preclinical studies have demonstrated that STN-DBS can attenuate the degeneration of a relatively intact nigrostriatal system from dopamine (DA)-depleting ...

Dopamine is transported into synaptic vesicles by the vesicular monoamine transporter (VMAT2; SLC18A2). Disruption of dopamine storage has been hypothesized to damage the dopamine neurons that are lost in Parkinson's disease. By disrupting vesicular storage of dopamine and other monoamines, we have created a ...

Dopamine is transported into synaptic vesicles by the vesicular monoamine transporter (VMAT2; SLC18A2). Disruption of dopamine storage has been hypothesized to damage the dopamine neurons that are lost in Parkinson's disease. By disrupting vesicular storage of dopamine and other monoamines, we have created a ...

In Parkinson's disease, cell death is selectively induced in mesencephalic nigral dopaminergic neurons. At present, no disease modifying therapy or radical treatment has been found for this disease. Some dopamine agonists may have a neuroprotective action in cultured cells and animal models. In the present study, we examined stimulating effects of a ...

The three main dopamine cell groups of the brain are located in the substantia nigra (A9), ventral tegmental area (A10), and retrorubral field (A8). Several subdivisions of these cell groups have been identified in rats and humans but have not been well described in mice, despite the increasing use of mice in neurodegenerative models ...

In the present study, an attempt has been made to explore the neuroprotective and neurorescue effects of nerve growth factor (NGF) on grafted cells and on host nigral dopaminergic neurons, respectively. NGF was co-transplanted with fetal ventral mesencephalic cells (VMC) in the striatum of 6-hydroxydopamine (6-OHDA) lesioned rat model of Parkinson's disease (PD). In the other ...

The effects of a partial hemitransection at the meso-diencephalic level, with or without chronic ganglioside GMI treatment, have been evaluated on striatal polyamine levels, 7, 14 and 21 days after lesion, as well as on the ability of the polyamine synthesis inhibitor alpha-difluoromethylornithine (alpha-DFMO) to modulate the protective effects of chronic ganglioside GMI treatment against ...

Antipsychotic drugs alter the activity of dopamine neurons in the ventral tegmental area (A10) and substantia nigra pars compacta (A9). As there is a dense projection of orexin neurons from the lateral hypothalamus to A10 dopaminergic neurons, and some antipsychotics have been shown to increase the expression of c-fos in ...

The central dopaminergic effects of an abeorphine derivative 201-678 were compared to those of apomorphine and bromocriptine in different model systems. After oral administration, this compound induced contralateral turning in rats with 6-hydroxydopamine induced nigral lesions and exhibited strong anti-akinetic properties in rats with 6-hydroxydopamine induced hypothalamic ...

Synapsins are a family of synaptic vesicle proteins that are important for neurotransmitter release. Here we have used triple knockout (TKO) mice lacking all three synapsin genes to determine the roles of synapsins in the release of two monoamine neurotransmitters, dopamine and serotonin. Serotonin release evoked by electrical stimulation was identical in substantia nigra pars ...

Intrastriatal application of 6-hydroxydopamine (6-OHDA) initiates a delayed and progressive loss of nigral dopaminergic neurons and therefore may better resemble the slowly developing neuropathology of Parkinson's disease. We investigated the anatomical, behavioural and biochemical consequences of intrastriatal 6-OHDA after prior labelling of nigral ...

Expression of brain-derived neurotrophic factor (BDNF) in the ventral mesencephalon has been assayed by mRNA in situ hybridization in adult rats with unilateral injections of 6-hydroxydopamine in the substantia nigra. On contralateral control sides, a specific hybridization signal was detected in the substantia nigra pars compacta (A9), ventral tegmental ...

Oxidative injury has been implicated in the etiology of Parkinson's disease (PD). Gypenosides (GPs), the saponins extract derived from the Gynostemma pentaphyllum, has various bioactivities. In this study, GPs was investigated for its neuroprotective effects on the 1-methyl-4-phenylpyridinium ion (MPP(+))-induced oxidative injury of dopaminergic neurons in primary nigral ...

Putamen 18F-dopa uptake of patients with Parkinson's disease (PD) is reduced by at least 35% at onset of symptoms; therefore, positron-emission tomography (PET) can be used to detect preclinical disease in clinically unaffected twins and relatives of patients with PD. Three out of 6 monozygotic and 2 out of 3 dizygotic unaffected PD co-twins have shown reduced putamen 18F-dopa uptake to ...

Putamen 18F-dopa uptake of patients with Parkinson's disease (PD) is reduced by at least 35% at onset of symptoms; therefore, positron-emission tomography (PET) can be used to detect preclinical disease in clinically unaffected twins and relatives of patients with PD. Three out of 6 monozygotic and 2 out of 3 dizygotic unaffected PD co-twins have shown reduced putamen 18F-dopa uptake to ...

Dopamine deficiency associated with Parkinson�s disease (PD) results in numerous changes in striatal transmitter function and neuron morphology. Specifically, there is marked atrophy of dendrites and dendritic spines on striatal medium spiny neurons (MSN), primary targets of inputs from nigral dopamine and cortical glutamate neurons, ...

Striatal particulate preparations, both from rats with lesion-induced striatal dopamine (DA) loss and from some striatal dopamine (DA) loss and from some patients with Parkinson's disease, exhibit increased /sup 3/H-neuroleptic binding, which is interpreted to be the mechanism of denervation-induced behavioral supersensitivity to dopaminergic ...

While intrastriatal transplants of dopamine-rich ventral mesencephalic tissue are effective in reversing a variety of drug-induced behaviors in the rat Parkinson model, previous studies have failed to obtain significant graft-induced effects on deficits in certain aspects of complex sensorimotor behaviors. In the present study we have applied a modified cell suspension ...

The protective effect of an iridoid catalpol extracted and purified from the traditional Chinese medicinal herb Rehmannia glutinosa on the neuronal degeneration of nigral-striatal dopaminergic pathway was studied in a chronic 1-methyl-4-phenyl-1,2,3,4-tetrahydropyridine (MPTP)/probenecid C57BL/6 mouse model and in 1-methyl-4-phenylpyridimium (MPP(+)) intoxicated cultured ...

Although the increased prevalence of Parkinson's disease (PD) with aging suggests that aging processes predispose dopamine neurons to degeneration, the mechanism involved remains unknown. Dopamine neurons contain significant amounts of neuromelanin, and the amount of neuromelanin increases with aging. In the present study, age-related changes in the number ...

Nitrogen pressure exposure in rats results in decreased dopamine (DA) release at the striatal terminals of the substantia nigra pars compacta (SNc) dopaminergic neurons, demonstrating the narcotic potency of nitrogen. This effect is attributed to decreased excitatory and increased inhibitory inputs to dopaminergic neurons, involving a change in NMDA and GABA(A) receptor ...

BackgroundSporadic Parkinson's disease (PD) is a progressive neurodegenerative disorder with unknown cause, but it has been suggested that neuroinflammation may play a role in pathogenesis of the disease. Neuroinflammatory component in process of PD neurodegeneration was proposed by postmortem, epidemiological and animal model studies. However, it remains unclear how neuroinflammatory factors ...

Although epidermal growth factor (EGF) receptor (ErbB1) is implicated in Parkinson's disease and schizophrenia, the neurotrophic action of ErbB1 ligands on nigral dopaminergic neurons remains controversial. Here, we ascertained colocalization of ErbB1 and tyrosine hydroxylase (TH) immunoreactivity and then characterized the neurotrophic effects of ErbB1 ligands on this cell ...

The motor abnormalities of Parkinson's disease (PD) are caused by alterations in basal ganglia network activity, including disinhibition of the subthalamic nucleus (STN), and excessive activity of the major output nuclei. Using adeno-associated viral vector-mediated somatic cell gene transfer, we expressed glutamic acid decarboxylase (GAD), the enzyme that catalyzes synthesis of the ...

Parkinson's disease (PD) is the second most common neurodegenerative disease worldwide, classically characterized by a triad of motor features: bradykinesia, rigidity and resting tremor. Neurodegeneration in PD critically involves the dopaminergic neurons of the substantia nigra pars compacta, which results in a severe reduction in dopamine levels in the dorsal striatum. ...

BackgroundMechanisms whereby gene�environment interactions mediate chronic, progressive neurodegenerative processes in Parkinson�s disease (PD)�the second most common neurodegenerative disease�remain elusive.ObjectiveWe created a two-hit [neuroinflammation and mutant ?-synuclein (?-syn) overexpression] animal model to investigate mechanisms through which mutant ?-syn and inflammation work ...

A unilateral 6-hydroxydopamine (6-OHDA)-lesioned rat model of Parkinson's disease was used to determine an effective dose to abolish circling behaviour of the continuous intrastriatal infusions of L-dopa via osmotic minipumps into the lesioned striatum. This 2-week L-dopa treatment evoked a dose-dependent decrease in the contralateral rotations induced by acute intraperitoneal L-dopa and carbidopa ...

Quantitative autoradiography using (/sup 3/H)-SCH 23390, (/sup 3/H)-sulpiride and (/sup 3/H)-forskolin was used to assess the effects of single and combined neurotoxin lesions of the nigrostriatal pathway in the rat brain on dopamine (DA) receptor subtypes and adenylate cyclase (AC), respectively. Ibotenic acid (IA) lesions of the caudate-putamen (CPu) resulted in near total ...

BackgroundParkinson's disease is a neurodegenerative disorder characterized pathologically by the loss of nigrostriatal dopamine neurons that project from the substantia nigra in the midbrain to the putamen and caudate nuclei, leading to the clinical features of bradykinesia, rigidity, and rest tremor. Oxidative stress from oxidized dopamine and related ...

The organic pesticide rotenone is a neurotoxin suspected to cause Parkinson's disease (PD) symptoms by selectively targeting and compromising the survival of dopaminergic neurons. Rotenone in rodent models reproduces key features of human PD by impairing the mitochondrial electron transport chain, leading to intracellular alpha-synuclein aggregates and functional impairments typical for PD. The ...

In vitro and in vivo electrophysiological studies have been used to assess the effects of glutamate, as well as specific agonists and antagonists for ionotropic, N-methyl-D-aspartate (NMDA), (R,S)-alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) and kainate, and metabotropic subtypes of the glutamate receptor, on the neuronal firing activity of midbrain, substantia nigra zona ...

We examined whether dopamine-degrading activity of monoamine oxidase (MAO) is present in dopaminergic neurons of the rat brain. We employed a double-labeling procedure combining immunohistochemistry for tyrosine hydroxylase (TH) and enzyme histochemistry for MAO activity using dopamine as a substrate. The following dopaminergic cell groups were examined: ...

Loss of dopamine neurons in experimental parkinsonism results in altered cyclic nucleotide cAMP and cGMP levels throughout the basal ganglia. Our objective was to examine whether expression of phosphodiesterase 10A (PDE10A), an isozyme presenting a unique distribution in basal ganglia, is altered after unilateral injection of 6-hydroxydopamine in the medial forebrain bundle, ...

The basal ganglia have a local renin-angiotensin system and it has been shown that the loss of dopaminergic neurons induced by neurotoxins is amplified by local angiotensin II (AII) via angiotensin type 1 receptors (AT1) and nicotinamide adenine dinucleotide phosphate (NADPH) complex activation. Recent studies have revealed a high degree of counter-regulatory interactions between ...

PREVIOUS WORK HAS SHOWN THE FUNCTIONS ASSOCIATED WITH ACTIVATION OF DOPAMINE PRESYNAPTIC RECEPTORS IN SOME SUBSTANTIA NIGRA PARS RETICULATA (SNR) AFFERENTS: (i) striatonigral terminals (direct pathway) posses presynaptic dopamine D(1)-class receptors whose action is to enhance inhibitory postsynaptic currents (IPSCs) and GABA transmission. (ii) ...

The treatment of the motor symptoms of Parkinson's disease (PD) is dependent on the use of dopamine replacement therapy in the form of L: -dopa and dopamine agonist drugs. However, the development of dyskinesia (chorea, dystonia, athetosis) can become treatment limiting. The initiation of dyskinesia involves a priming process dependent on the presence of ...

Whereas dopamine agonists are known to provide symptomatic benefits for Parkinson's disease, recent clinical trials suggest that they might also be neuroprotective. Laboratory studies demonstrate that dopamine agonists can provide neuroprotective effects in a number of model systems, but the role of receptor-mediated signalling in these effects is ...

This aim of this chapter is to review literature on the excitability and function of dopamine neurons that originate in the midbrain and project to cortico-limbic and motor structures (A9 and A10 dopamine pathways). Electrophysiological studies on rodent or non-human primates have shown that these ...

Estrogen modulates dopamine synthesis, release, and metabolism in corticolimbic and striatal targets of midbrain dopamine neurons. The relevant sites of receptor-mediated action, however, had been elusive, because all available evidence suggested a paucity of intracellular estrogen receptors in the A8, A9, and A10 ...

The mesotelencephalic dopamine system shows substantial genetic variation which fundamentally affects normal and pathological behaviors related to motor function, motivation, and learning. Our earlier radioenzyme assay studies demonstrated significantly higher activity of tyrosine hydroxylase (TH), the first and rate limiting enzyme in the biosynthesis of catecholamine ...

7-Hydroxy-N,N-di-n-propyl-2-aminotetralin (7-OH-DPAT), an agonist with relative selectivity for the dopamine D3 receptor, was examined in several electrophysiological assays to determine whether it exhibits preferential effects in the mesolimbic versus nigrostriatal dopamine systems. Extracellular single unit activities of substantia nigra pars compacta ...

BackgroundMissense mutations and multiplications of the ?-synuclein gene cause autosomal dominant familial Parkinson's disease (PD). ?-Synuclein protein is also a major component of Lewy bodies, the hallmark pathological inclusions of PD. Therefore, ?-synuclein plays an important role in the pathogenesis of familial and sporadic PD. To model ?-synuclein-linked disease in vivo, transgenic mouse ...

In many everyday settings, the relationship between our choices and their potentially rewarding outcomes is probabilistic and dynamic. In addition, the difficulty of the choices can vary widely. Although a large body of theoretical and empirical evidence suggests that dopamine mediates rewarded learning, the influence of dopamine in probabilistic and ...

Utilizing behavioral, biochemical and electrophysiological methods, central effects of the monoamine oxidase-B inhibitor deprenyl (selegiline) were analyzed. Administration of deprenyl (3-30 mg/kg, i.p.) caused a dose-dependent increase in the spontaneous locomotor activity. In the striatum, deprenyl (10 and 30 mg/kg) changed the dopa accumulation following 3-hydroxybenzylhydrazine hydrochloride ...

The positron emission tomography (PET) tracer 2?-carbomethoxy-3?-(4-chlorophenyl)-8-(2-[18F]-fluoroethyl)-nortropane ((18)F-FECNT) is a highly specific ligand for dopamine transporter (DAT) that yields higher peak striatum-to-cerebellum ratios and offers more favorable kinetics than most (18)F-radiolabeled DAT ligands currently available. The goal of this study is to validate ...

The endogenous cannabinoid system is a new signaling system composed by the central (CB1) and the peripheral (CB2) receptors, and several lipid transmitters including anandamide and 2-arachidonylglycerol. This system is the target of natural cannabinoids, the psychoactive constituents of Cannabis sativa preparations (marijuana, hashish). Acute and chronic cannabis exposure has been associated with ...

DCC (deleted in colorectal cancer)-the receptor of the netrin-1 neuronal guidance factor-is expressed and is active in the central nervous system (CNS) during development, but is down-regulated during maturation. The substantia nigra contains the highest level of netrin-1 mRNA in the adult rodent brain, and corresponding mRNA for DCC has also been detected in this region but has not been localized ...