23 resultados para Dopamine transporter

em Repositório Institucional UNESP - Universidade Estadual Paulista "Julio de Mesquita Filho"


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Diethylpropion (DEP) is an amphetamine-like agent used as an anorectic drug. Abuse of DEP has been reported and some restrictions of its use have been recently imposed. The conditioning place preference (CPP) paradigm was used to evaluate the reinforcing properties of DEP in adult male Wistar rats. After initial preferences were determined, animals weighing 250-300 g (N = 7 per group) were conditioned with DEP (10, 15 or 20 mg/kg). Only the dose of 15 mg/kg produced a significant place preference (358 ± 39 vs 565 ± 48 s). Pretreatment with the D1 antagonist SCH 23390 (0.05 mg/kg, sc) 10 min before DEP (15 mg/kg, ip) blocked DEP-induced CPP (418 ± 37 vs 389 ± 31 s) while haloperidol (0.5 mg/kg, ip), a D2 antagonist, 15 min before DEP was ineffective in modifying place conditioning produced by DEP (385 ± 36 vs 536 ± 41 s). These results suggest that dopamine D1 receptors mediate the reinforcing effect of DEP

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Dopamine (DA) is known as a primary regulator of prolactin secretion (PRL) and angiotensin II (Ang II) has been recognized as one brain inhibitory factor of this secretion. In this work, estrogen-primed or unprimed ovariectornized rats were submitted to the microinjection of saline or Ang II after previous microinjection of saline or of da antagonist (haloperidol, sulpiride or SCH) both in the medial preoptic area (MPOA). Our study of these interactions has shown that 1) estrogen-induced PRL secretion is mediated by Ang II and da actions in the MPOA, i.e. very high plasma PRL would be prevented by inhibitory action of Ang II, while very low levels would be prevented in part by stimulatory action of da through D-2 receptors, 2) the inhibitory action of Ang II depends on estrogen and is mediated in part by inhibitory action of da through D, receptors and in other part by inhibition of stimulatory action of da through D2 receptors.

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Fencamfamine (FCF) is a psychostimulant drug classified as an indirect dopamine agonist. In the present study we evaluated the daily variation in plasma FCF concentration and in striatal dopamine receptors. Adult male Wistar rats (250-300 g) maintained on a 12-h light/12-h dark cycle (lights on at 07:00 h) were used. Rats received FCF (10.0 mg/kg, ip) at 09:00, 15:00, 21:00 or 03:00 h and blood samples were collected 30 (N = 6) or 60 (N = 6) min after the injections. Plasma FCF was measured by gas chromatography using an electron capture detector. Two-way ANOVA showed significant differences in FCF concentration when blood samples were collected 30 min after the injection, and the highest value was obtained following injection 21:00 h. Moreover, at 15:00, 21:00 and 03:00h, plasma FCF levels were significantly lower 60 min after injection when compared to the 30-min interval. Two other groups of rats (N = 6) were decapitated at 09:00 or 21:00 h and the striata were dissected for the binding assays. The Bmax for [H-3]-spiroperidol binding to striatal membranes was higher at 21:00 h, without changes in affinity constant (Kd). In conclusion, plasma FCF levels and dopamine receptors undergo daily variation,a phenomenon that should be considered to explain the circadian time-dependent effects of FCF.

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To evaluate the effects of acepromazine maleate on the cardiovascular changes induced by dopamine in isoflurane-anesthetized dogs.Prospective, randomized cross-over experimental design.Six healthy adult spayed female dogs weighing 16.4 +/- 3.5 kg (mean +/- SD).Each dog received two treatments, at least 1 week apart. Acepromazine (0.03 mg kg(-1), IV) was administered 15 minutes before anesthesia was induced with propofol (7 mg kg(-1), IV) and maintained with isoflurane (1.8% end-tidal). Acepromazine was not administered in the control treatment. Baseline cardiopulmonary parameters were measured 90 minutes after induction. Thereafter, dopamine was administered intravenously at 5, 10, and 15 mu g kg(-1) minute(-1), with each infusion rate lasting 30 minutes. Cardiopulmonary data were obtained at the end of each infusion rate.Dopamine induced dose-related increases in cardiac index (CI), stroke index, arterial blood pressure, mean pulmonary arterial pressure, oxygen delivery index (DO2I) and oxygen consumption index. In the control treatment, systemic vascular resistance index (SVRI) decreased during administration of 5 and 10 mu g kg(-1) minute(-1) of dopamine and returned to baseline with the highest dose (15 mu g kg (-1) minute(-1)). After acepromazine treatment, SVRI decreased from baseline during dopamine administration, regardless of the infusion rate, and this resulted in a smaller increase in blood pressure at 15 mu g kg (-1) minute(-1). During dopamine infusion hemoglobin concentrations were lower following acepromazine and this contributed to significantly lower arterial O-2 content.Acepromazine prevented the return in SVRI to baseline and reduced the magnitude of the increase in arterial pressure induced by higher doses of dopamine. However, reduced SRVI associated with lower doses of dopamine and the ability of dopamine to increase CI and DO2I were not modified by acepromazine premedication.Previous acepromazine administration reduces the efficacy of dopamine as a vasopressor agent in isoflurane anesthetized dogs. Other beneficial effects of dopamine such as increased CO are not modified by acepromazine.

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To identify genes specifically or predominantly expressed in the stigmas/styles and to establish their possible function in the reproductive process of plants, a tobacco stigma/style cDNA library was constructed and differentially screened, resulting in the isolation of several cDNA clones. The molecular characterization of one of these clones is described here. After sequencing the cDNA and the isolated genomic clone, it was determined that the corresponding gene encodes a protein containing an ATP-binding cassette, characteristic of ABC transporters. This gene, designated as NtWBC1 (Nicotiana tabacum ABC transporter of the White-Brown Complex subfamily), encodes a protein that contains the typical structure of the 'half-transporters' of the White subfamily. To establish the spatial expression pattern of the NtWBC1 gene, northern blot and real-time RT-PCR analyses with total RNA from roots, stems, leaves, sepals, petals, stamens, stigmas/styles, ovaries, and seeds were performed. The result revealed a transcript of 2.5 kb present at high levels in stigmas and styles and a smaller transcript (2.3 kb) present at a lower level in stamens. NtWBC1 expression is developmentally regulated in stigmas/styles, with mRNA accumulation increasing toward anthesis. In situ hybridization experiments demonstrated that NtWBC1 is expressed in the stigmatic secretory zone and in anthers, at the stomium region and at the vascular bundle. NtWBC1 is the first ABC transporter gene with specific expression in plant reproductive organs to be identified and its expression pattern suggests important role(s) in the reproductive process.

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The effects of prenatal exposure of rat pups to 0.08 mg/kg deltamethrin (DTM) on physical, reflex and behavioral developmental parameters, on forced swimming and open-field behaviors, and on striatal monoamine levels at 60 days of age were observed. Maternal and offspring body weight, physical and reflex development were unaffected by the exposure to the pesticide. At 21 days of age, open-field locomotion frequency and immobility duration of male and female offspring were not different between control and exposed animals. However, male rearing frequency was increased in experimental animals. A decreased immobility latency to float and in general activity after the swimming test in male offspring was observed at adult age; no interference was detected in the float duration during the swimming test. In addition, these animals presented higher striatal 3,4-dihydroxyphenylacetic acid (DOPAC) levels without modification in dopamine (DA) levels and an increased DOPAC/DA ratio. These data indicate a higher activity of the dopaminergic system in these animals. Noradrenaline (NA) levels were increased, while MHPG levels were not detectable in the system studied. Serotonin (5-HT) and 5-hydroxyindolacetic acid (5-HIAA) levels, as well as the homovanillic acid (HVA)/DA ratio, were not modified by the exposure to the pesticide. No changes were observed in swimming and open-field behaviors nor were there any changes in striatal monoamines or their metabolites in the female experimental group. In relation to the pesticide formula, the present data showing that prenatal exposure to DTM alters latency to float and the activity of striatal dopaminergic system might reflect a persistent effect of the pesticide on animal motor activity, mainly in males. on the other hand, the decrease in general activity observed in experimental male rats suggests higher levels of emotionality induced by previous exposure to the swimming behavior test in relation to control animals. Data gathered in the present study may be important for the assessment of the safety of pyrethroid insecticides. (C) 2001 Elsevier B.V. All rights reserved.

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The electrocatalysis of dopamine has been studied using a cobalt hexacyanoferrate film (CoHCFe)-modified glassy carbon electrode. Using a rotating disk CoHCFe-modified electrode, the reaction rate constant for dopamine was found to be 3.5 x 105 cm(3) mol(-1) s(-1) at a concentration of 5.0 x 10(-5) mol L-1. When a Nafion (R) film is applied to the CoHCFe-modified electrode surface a high selectivity for the determination of dopamine over ascorbic acid was obtained. The analytical curve for dopamine presented linear dependence over the concentration range from 1.2 x 10(-5) to 5.0 x 10(-4) mol L-1 with a slope of 23.5 mA mol(-1) L and a linear correlation coefficient of 0.999. The detection limit of this method was 8.9 x 10(-6) mol L-1 and the relative standard deviation for five measurements of 2.5 x 10(-4) mol L-1 dopamine was 0.58%.

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Fencamfamine (FCF) is a psychostimulant classified as an indirect dopamine agonist. The conditioning place preference (CPP) paradigm was used to investigate the reinforcing properties of FCF. After initial preferences had been determined, animals were conditioned with FCF (1.75, 3.5, or 7.0 mg/kg; IP). Only at the dose of 3.5 mg/kg FCF produced a significant place preference. Pretreatment with SCH23390 (0.05 mg/kg, SC) or naloxone (1.0 mg/kg SC) 10 min before FCF (3.5 mg/kg; IP) blocked both FCF-induced hyperactivity and CPP. Pretreatment with metoclopramide (10.0 mg/kg; IP) or pimozide (1.0 mg/kg, IP), respectively, 30 min or 4 h before FCF (3.5 mg/kg; IP), which blocked the FCF-induced locomotor activity, failed to influence place conditioning produced by FCF. In conclusion, the present study suggests that dopamine D 1 and opioid receptors are related to FCF reinforcing effect, while dopamine D 2 subtype receptor was ineffective in modifying FCF-induced CPP.