It is important to elucidate the mechanism of dysautonomias in patients with Parkinson's disease; therefore, this study aimed to investigate the cardiovascular and autonomic changes that occur in an animal model of Parkinsonism. Adult male Wistar rats were anesthetized before bilateral microinfusions of 6-hydroxydopamine (6-OHDA) into the substantia nigra. The sham group underwent the same surgical procedure but received vehicle. After 7 days, the mean arterial pressure (MAP) and heart rate (HR) were measured, and various drugs were injected into conscious rats through cannulas previously implanted in the femoral artery and vein. Spectral analyses of systolic arterial pressure (SAP) and pulse interval (PI) were conducted with the CardioSeries software as the spontaneous baroreflex gain and effectivity. The animals were subjected to ␣-, ␤-adrenergic, or muscarinic receptor antagonism. For confirmation of the lesion, the levels of dopamine in the striatum were quantified by high-performance liquid chromatography. Animals that underwent 6-OHDA microinfusion had lower MAP and HR compared with those in the sham group. Spectral analysis of SAP showed that 6-OHDA animals exhibited a decrease in the sympathetic component. The PI values did not differ between groups. After the administration of muscarinic and ␤-adrenergic antagonists, the cardiovascular measures did not differ between the groups. However, upon administration of the ␣-adrenergic antagonist, the 6-OHDA animals exhibited a lower decrease in the MAP. We report cardiovascular impairments in 6-OHDA animals, possibly due to decreased sympathetic activity. Determination of the origin of these changes (central or peripheral) requires further investigation. sympathetic; parasympathetic; prazosin; spectral analysis; dopamine; baroreflex PARKINSON'S DISEASE (PD) is characterized by a decrease in striatal dopamine (DA) levels due to the death of neurons in the substantia nigra pars compacta (SNpc). After an 80% decrease of DA levels in the striatum, the classic motor symptoms of PD appear (11,38). These include bradykinesia, rigidity, tremor, and postural instability (29). Although the motor signs of PD are well studied and recognized, symptoms of dysautonomia, despite being reported at all stages of PD, are rarely considered clinically even if they are the main complaint. Dysautonomia considerably impairs the quality of life in the early stages, and it can be debilitating with advancing disease (7,8).Cardiovascular involvement is very common in patients with PD (21, 24). Orthostatic hypotension (OH), postprandial hypotension, as well as cardiac arrhythmias, livedo reticularis, and leg edema are commonly reported (26,43). OH is the most reported symptom with a prevalence of up to 58% in patients with PD (18,24). However, despite all of the speculation, the pathophysiology of OH, as well as the severity of hemodynamic compromise, remains controversial. This has been associated with a central disorder that impacts the medulla, namely, the involvement of both the centra...

Rotenone exposure in rodents provides an interesting model for studying mechanisms of toxin-induced dopaminergic neuronal injury. However, several aspects remain unclear regarding the effects and the accuracy of rotenone as an animal model of Parkinson's disease (PD). In order to counteract these limitations, this study characterized a precise neurotoxin-delivery strategy employing the bilateral intranigral administration protocol of rotenone as a reliable model of PD. We performed bilateral intranigral injections of rotenone (12 μg) and subsequent general activity (1, 10, 20, and 30 days after rotenone) and cognitive (7, 8, 15, and 30 days after rotenone) evaluations followed by neurochemical and immunohistochemical tests. We have observed that rotenone was able to produce a remarkable reduction on the percentage of tyrosine hydroxylase immunoreactive neurons (about 60%) within the substantia nigra pars compacta. Dopamine (DA) was severely depleted at 30 days after rotenone administration, similarly to its metabolites. In addition, an increase in DA turnover was detected at the same time-point. In parallel, striatal serotonin and its metabolite were found to be increased 30 days after the neurotoxic insult, without apparent modification in the serotonin turnover. Besides, motor behavior was impaired, mainly 1 day after rotenone. Furthermore, learning and memory processes were severely disrupted in different time-points, particularly at the training and test session (30 days). We now provide further evidence of a time-dependent neurodegeneration associated to cognitive impairment after the single bilateral intranigral administration of rotenone. Thus, it is proposed that the current rotenone protocol provides an improvement regarding the existing rotenone models of PD.

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The current investigation compared intranigral lipopolysaccharide (LPS), 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) and 6-hydroxydopamine (6-OHDA) administrations, in the light of neurochemical, behavioral and endogenous antioxidant glutathione alterations. All the results were collected 1, 3 and 7 days after the lesions. LPS produced a delayed reduction of striatal dopamine, whereas homovanillic acid was drastically increased at the first time-point. Comparatively, MPTP promoted dopamine reduction 3 and 7 days with increase of homovanillic acid. Whilst, 6-OHDA generated initial increase of dopamine and homovanillic acid followed by subsequent decrease of this neurotransmitter accompanied by reductions of dopamine metabolites at the same periods. Furthermore, nigral glutathione demonstrated to be a far more sensitive target for LPS than for MPTP or 6-OHDA. Behavioral data indicated impairments induced by MPTP, 6-OHDA but not LPS. In conclusion, it is suggested that intranigral LPS can provide new insights about neuroinflammation, simulating features of the pre-motor phase of Parkinson's disease.