1,721,661 research outputs found
Effect of PSK 3668 on SKF 38393-induced Fos expression.
No full text<p>SKF 38393 increased Fos expression within the AVPV, CPu, BST, mPOA, CeA, VMH, Arc, and Hb, but not within the PVP. Pretreatment with PSK 3668 partially blocked SKF 38393-induced Fos expression within the BST and CeA. Data are shown as mean±standard error. Within each brain region, bars not denoted by the same letter are statistically different (p<0.05).</p
Motor activity following the administration of selective D-1 and D-2 dopaminergic drugs to MPTP-treated common marmosets
No full textThe ability of selective D-1 agonist and antagonist drugs to alter motor deficits and locomotor activity was studied in MPTP-treated common marmosets. Both the D-2 agonist quinpirole and the mixed D-1/D-2 agonist apomorphine reversed the motor impairments and induced locomotor activity. The D-1 antagonist SCH 23390 and the D-2 antagonist raclopride given alone further reduced motor function in MPTP-treated animals. The actions of quinpirole were potently and completely inhibited by raclopride but only partially and inconsistently by SCH 23390. In contrast, the effects of apomorphine were markedly but incompletely inhibited by both raclopride and SCH 23390. The D-1 agonist SKF 38393 alone caused a dose related reduction in motor activity. SKF 38393 weakly and partially inhibited the improvements in motor function produced by quinpirole but had a more pronounced effect on apomorphine induced motor activity. The induction of motor activity in MPTP treated common marmosets may separately involve both D-1 and D-2 receptors. Comparison with our previous data on the effect of the same drugs in normal common marmosets provides some evidence for a breakdown of linkage between D-1 and D-2 systems following MPTP treatment. The actions of SKF 38393 in MPTP-treated common marmosets contrasts with its ability to induce behavioural activation and a facilitation of D-2 mediated behaviour in rodents. SKF 38393 may not be the compound with which to delineate the role of D-1 receptors in primates
Gastric and Duodenal Anti-ulcer Activity of SKF 38393, a Dopamine D1-Receptor Agonist in Rats
No full textAbstract
The effect of SKF 38393 (1-phenyl-7,8-diol-2,3,4,5-tetrahydro-1H-3-benzazepine), a specific dopamine D1-receptor agonist, was studied on pylorus-ligation and water immersion plus restraint stress-induced gastric ulcers, and cysteamine-induced duodenal ulcers in rats.
Repeated administration of SKF 38393 (5 and 10 mg kg−1, p.o.) for six days was found to be effective in the prevention of gastric ulceration induced by water immersion plus restraint stress in rats. In 19-h pylorus-ligated rats, repeated treatment with SKF 38393 showed a significant reduction in the number and severity of ulcers. SKF 38393 did not alter the total gastric-mucosal carbohydrates: protein ratio; however, the gastric content volume and the free and total acidity were significantly reduced. In cysteamine-induced duodenal ulcers, the treatment with SKF 38393 for 6 days prevented the duodenal lesions.
Our data suggests the involvement of dopamine D1 receptors in the anti-ulcer activity of SKF 38393, which could be largely attributed to its anti-secretory effect. Its anti-ulcer activity against water immersion plus restraint, also points towards a central mode of action, but its failure to alter the carbohydrate: protein ratio rules out any protective effect through the strengthening of the gastric mucosal barrier.</jats:p
Ontogenetic SKF 38393 Treatments Sensitize Dopamine D\u3csub\u3e1\u3c/sub\u3e Receptors in Neonatal 6-OHDA-Lesioned Rats
No full textNeonatal 6-hydroxydopamine (6-OHDA) treatment of rats is associated with supersensitization of the dopamine (DA) D1 agonist induction of stereotyped and locomotor behaviors. The present study was conducted to determine whether ontogenetic treatments of these rats with the DA D1 receptor agonist, SKF 38393, would produce a maximal DA D1 receptor supersensitivity, as measured by locomotor behavior in adulthood. Rat pups were treated daily with SKF 38393-HCl (3.0 mg/kg per day, i.p.) or saline vehicle for 28 consecutive days from birth. These animals were additionally treated at 3 days after birth with 6-OHDA-HBr (100 μg, in each lateral ventricle, salt form) or its vehicle. Between 6 and 9 weeks locomotor activity or stereotyped behaviors were observed after weekly challenge doses of SKF 38393-HCl (3.0 mg/kg, i.p.). In the neonatal 6-OHDA group, successive SKF 38393 treatments produced progressively greater locomotor activity. In the group of rats treated during postnatal ontogeny with both 6-OHDA and SKF 38393 daily treatments, the first adult challenge dose of SKF 38393 produced an enhanced locomotor response, greater than that seen in other groups (P \u3c 0.01). Subsequent SKF 38393 treatments of this group produced increasingly greater locomotor responses. SKF 38393-induced stereotyped behavioral effects were greater in the 6-OHDA-lesioned groups, whether or not SKF 38393 was administered ontogenetically. Profound reductions (\u3e 99%) of DA and its metabolites were found in the striatum of neonatal 6-OHDA treated rats, regardless of whether SKF 38393 was co-administered ontogenetically. A marked elevation in striatal 5-HT (\u3e 50%) accompanied the DA depletion in the striatum. These findings indicate that neonatal 6-OHDA treatment produces the expected destruction of striatal DA fibers with associated sprouting of 5-HT fibers, while repeated ontogenetic treatments of these rats with a D1 agonist produces partial sensitization of the DA D1 receptors in adulthood
Comparison of the discriminative-stimulus effects of SKF 38393 with those of other dopamine receptor agonists
No full textThe dopamine D(1)-like receptor agonists have traditionally been defined molecularly by their efficacy in stimulating adenylyl cyclase. However, evidence correlating the effectiveness of these drugs in behavioral assays and their effectiveness biochemically has not been forthcoming. The present study compared the discriminative-stimulus effects of the D(1)-like partial agonist SKF 38393 with several other D(1)-like agonists, an indirect agonist, cocaine, and a D(2)-like agonist, quinpirole. Rats were trained under a fixed-ratio 30-response schedule to discriminate SKF 38393 (5.6 mg/kg) from vehicle. Under this schedule, 30 consecutive responses on one of two keys were reinforced with food presentation after a pre-session injection of 5.6 mg/kg SKF 38393, and 30 consecutive responses on the alternative key were reinforced after saline injection. When daily performances were stable, substitution patterns for several compounds were assessed during test sessions in which 30 consecutive responses on either key were reinforced. Quinpirole and cocaine each produced saline-appropriate responding. In contrast, the D(1)-like agonists, SKF 75670 and SKF 77434, fully substituted for SKF 38393. Curiously, SKF 82958, which is considered a full agonist based on adenylyl cyclase assays, was less effective in substituting for SKF 38393 (maximum drug-appropriate responding 66%) than was the partial agonist SKF 75670. The present results suggest that second messenger effects other than stimulation of adenylyl cyclase may play an important role in the behavioral effects of dopamine D(1)-like agonists
Prenatal exposure to SKF-38393 alters the response to light of adult rats
No full textThe current study examined the consequences of prenatal SKF-38393 exposure on the cellular response in the adult suprachiasmatic nuclei to light. Pregnant rats were injected with the dopamine agonist SKF-38393 or vehicle daily from gestational day 15 to 21. Adult offspring received a light pulse (1 min/2 lux) 4 or 8 h after lights off (ZT16 or ZT20 where ZT = zeitgeber time). Brains were processed for c-FOS-like immunoreactivity in the SCN. At ZT20 the number of cells expressing c-FOS protein after a light pulse was the same in both groups. At ZT16 the number of cells in the SCN of SKF-38393-exposed animals was 58% lower than the vehicle-treated group. The data suggest that prenatal SKF-38393 treatment may have long-term consequences for SCN function.Sally A. Ferguson and David J. Kennawa
SKF 38393 and SCH 23390 Inhibit Reuptake of Serotonin by Rat Hypothalamic Synaptosomes
No full text<i>Background/Aims:</i> Both the dopamine receptor D<sub>1</sub> agonist SKF 38393 and the antagonist SCH 23390 are benzazepine derivatives that have been widely used as pharmacological tools and radioligands. Evidence suggests that behavioral effects of both compounds do not always correspond to their established receptor subtype selectivity. Here, we assessed the effects of SKF 38393 and SCH 23390 on the synaptosomal uptake of tritiated serotonin. <i>Methods:</i> Uptake experiments were performed by using [<sup>3</sup>H]serotonin and synaptosomal fractions prepared from the hypothalamus of rat brain. <i>Results:</i> Both SKF 38393 and SCH 23390 inhibited synaptosomal uptake of [<sup>3</sup>H]serotonin, with IC<sub>50</sub> values of 910 ± 60 nmol/l and 1,400 ± 80 nmol/l, respectively. Clomipramine, a known inhibitor of serotonin uptake, and (+)-amphetamine, a weak inhibitor, had IC<sub>50</sub> values of 14 ± 1 nmol/l and more than 10,000 nmol/l, respectively, under the same experimental conditions. The IC<sub>50</sub> values for SKF 38393 and SCH 23390 fall within the broad range of corresponding values for antidepressants that have been shown to inhibit the uptake of serotonin. This finding indicates that SKF 38393 and SCH 23390 can enhance the activity of the serotonergic system in the brain, a mechanism that may be responsible for some of the effects of these drugs. <i>Conclusion:</i> SKF 38393 and SCH 23390 are useful tools to differentiate D<sub>1</sub> from D<sub>2</sub> receptors, but their indirect effects on serotonergic mechanisms have to be considered.</jats:p
SKF 38393-induced Fos expression within the BST and mPoA.
No full text<p>Photomicrographs of SKF 38393-induced Fos expression within the BST and mPOA. The right column shows schematics of the regions pictured. Shaded area indicates regions examined. 3V, third ventricle; ac, anterior commissure; BST, bed nucleus of the stria terminalis; LV, lateral ventricle; mPOA, medial preoptic area.</p
SKF 38393 reverses cocaine-conditioned place preference in mice
No full textCocaine is a psychotropic drug with a high potential for abuse due to its euphoric effects. Efforts to develop medications for the treatment of cocaine dependence have not been clinically successful. Some studies using animal models have shown positive effects of dopaminergic agents such as partial agonists of the dopamine D1 receptor. Thus, this study aimed to examine the effect of the dopamine D1 receptor partial agonist SKF 38393 on cocaine craving. Adult male C57BL/6J mice were injected with cocaine for 10 days in a conditioned place preference apparatus using a biased procedure and subsequently treated for three consecutive days with SKF 38393. the results showed that SKF 38393 was able to block the preference of cocaine-conditioned animals for the compartment paired with the drug without showing effects on locomotor activity. the results of this study suggest that partial activation of D1 dopamine receptors may be necessary for the development of pharmacotherapies for cocaine addiction. (c) 2012 Elsevier Ireland Ltd. All rights reserved.Universidade Federal de São Paulo UNIFESP, Dept Psychobiol, São Paulo, BrazilUniv Fed Parana UFPR, Dept Pharmacol, Recife, PE, BrazilUniversidade Federal de São Paulo UNIFESP, Dept Psychobiol, São Paulo, BrazilWeb of ScienceAssociacao Fundo de Incentivo a Pesquisa (AFIP)Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)FAPESP: 09/16515-
Photomicrographs of SKF 38393-induced Fos expression within the mPOA.
No full text<p>PSK 3668 did not block SKF 38393-induced Fos expression within this region. A schematic of this region is shown in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0002177#pone-0002177-g002" target="_blank">Figure 2</a>. 3V, third ventricle.</p
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