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EN
5-HT2A/2C receptors are one of the most important in controlling basal ganglia outputs. In rodent models of Parkinson's disease (PD) blockade of these receptors increases locomotion and enhances the actions of dopamine (DA) replacement therapy. Moreover, previously we established that 5-HT2A/2C antagonist attenuate DA D1 agonist mediated vacuous chewing movements (VCMs) which are considered as an animal representation of human dyskinesia. These findings implicate 5-HT neuronal phenotypes in basal ganglia pathology, and promote 5-HT2 antagonists as a rational treatment approach for dyskinesia that is prominent in most instances of PD replacement therapy. In the current study we determined whether ketanserin (KET) and/or amphetamine (AMPH) affected dopaminergic neurotranssmision in intact and fully DA-denervated rats. Moreover, we looked into extraneuronal content of HO. of the neostriatum after AMPH and/or KET injection, assessed by HPLC analysis of dihydroxybenzoic acids (2,3- and 2, 5-DHBA) - spin trap products of salicylate. Findings from the present study demonstrated that there are no substantial differences in extraneuronal HO. generation in the neostriatum between control and parkinsonian rats. KET did not affect DA release in the fully DA-denervated rat's neostriatum and also did not enhance HO. production. As 5-HT2A/2C receptor-mediated transmission might prove usefulness not only in addressing motor complications of PD patients (dyskinesia) but also in addressing non-motor problems such depression and/or L-DOPA evoked psychosis, the findings from the current study showed that the use of 5-HT2A/2C receptor antagonists in Parkinson's disease does not impend the neostriatal neuropil to be damaged by these drugs. We concluded that 5-HT2A/2C receptor antagonists may provide an attractive non-dopaminergic target for improving therapies for some basal ganglia disorders.
EN
To determine the susceptibility of developing brain and other tissues to accumulate zinc, rats were exposed to zinc at different periods of ontogeny. For the prenatal group, pregnant Wistar rats received 50 ppm of zinc (ZnSO₄ · 7H₂O) in drinking for the entire duration of pregnancy. On the day of delivery zinc was removed from the drinking water. Another group, dams, received 50 ppm of zinc in drinking water only during the suckling period (from delivery until the 21st day of postnatal life). Their offspring were weaned on the 21st day, at which time zinc was removed from the drinking water. The control group drank tap water only. At 3 weeks after birth, the level of zinc was estimated in the brain, liver, mandibular bone and kidney of offspring from all groups. At 8 weeks after birth 6-[³H]D-glucose (500 µCi/kg) was administered IP to male offspring, 15 minutes before sacrifice. By liquid scintillation spectroscopy, ³H-activity (expressed as disintegrations per minute [DPM]) was determined in discrete parts of the brain and some peripheral tissues, and expressed as DPM/100 mg of tissue, wet weight. It was found that the highest amount of zinc was accumulated in the brain and liver of rat offspring that were exposed to zinc postnatally. [³H]-activity was at lower levels, in comparison, in nearly all other parts of the brain of rats exposed to zinc postnatally. In offspring receiving zinc prenatally, zinc levels were at similar or lower amounts in the brain and peripheral tissues, vs. the group with postnatal exposure. From this study in rats we conclude that zinc accumulates to the highest extent in brain, following a later ontogenetic (postnatal) exposure period, and by this, there is also greater disturbance of metabolic processes associated with glucose utilization.
EN
Pregnant Wistar rats received 50 ppm of zinc (ZnSO4 • 7H2O) in their drinking water for the entire duration of pregnancy. On the day of delivery zinc was removed from the drinking water. Another group, dams, received 50 ppm of zinc in drinking water during the suckling period (from delivery until the 21st day of postnatal life). Their offspring were weaned on the 21st day, at which time zinc was removed from the drinking water. The control group drank tap water only. In 8-12-week-old offspring of all three groups the DA, DOPAC, HVA, 3-MT, 5-HT, 5-HIAA, NA, and MOPEG synthesis rate in the brain was estimated by HPLC/ED technique. Independent behavioral exam were performed such as locomotor and exploratory activity, irritability, yawning and oral activity, stereotype behavior, catalepsy and others. For the above, cen­tral DA receptor agonists (quinpirole, SKF 38393, apomorphine, 7-OH-DPAT) or antagonists (haloperidol, SCH 23390) were used. It was found that exposure to zinc during early stages of ontogenic development produce changes in the central dopaminergic system activity of adult offspring. From the above we con­cluded that uncontrolled supplementation with zinc during pregnancy or lactation can induce disturbance of the central dopaminergic system in adult mammal.
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