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At least 1,099 records · Page 61Linked to original sources
PubMed1994

Direct in vivo evidence that D2 dopamine receptors can modulate dopamine uptake.

In vivo electrochemistry was used to determine the effects of locally applied raclopride (a D2 receptor antagonist) and SCH-23390 (a D1 receptor antagonist) on the clearance of locally applied dopamine in the striatum, nucleus accumbens, and medial prefrontal cortex of rats. Chronoamperometric recordings were continuously made at 5 Hz using Nafion-coated, single carbon fiber electrodes. When a calibrated amount of dopamine was pressure ejected at 5-min intervals from a micropipette adjacent (280-310 microns) to the electrode, transient and reproducible dopamine signals were detected in all three regions. Local application of raclopride from a second micropipette, prior to pressure ejection of dopamine, increased the amplitude and time course of the dopamine signals, indicating significant inhibition of the dopamine transporter. In contrast, local application of SCH-23390 or saline had no effect on the dopamine signals. These data indicate that D2, but not D1, dopamine receptors can modulate the activity of the dopamine transporter.

Animals↗
PubMed1994

GABAergic modulation of striatal peptide expression in rats and the alterations induced by dopamine antagonist treatment.

GABAergic modulation of enkephalin, substance P and glutamic acid decarboxylase (GAD67) gene expression and the alterations induced by dopamine receptor blockade were studied in the rat striatum. Following subchronic treatment with the GABA-A agonist muscimol, the GABA-B agonist baclofen or the GABA transaminase inhibitor gamma-vinyl GABA there were no significant changes in striatal peptide and GAD67 gene expression. Following repeated administration of the D-2 antagonists, eticlopride and haloperidol, there was an increase in enkephalin and GAD67 mRNA levels and parallel decrease in that of substance P. These were unaffected by co-administration of gamma-vinyl GABA. The D-1 antagonist, SCH 23390 administered alone or together with gamma-vinyl GABA did not alter peptide or GAD67 mRNA levels. It seems that pharmacological stimulation of GABA receptors has little effect on enkephalin, substance P or GAD67 mRNA expression in striatal output neurons.

Animals↗
PubMed1995

Clozapine decreases serotonin extracellular levels in the nucleus accumbens by a dopamine receptor-independent mechanism.

By using brain microdialysis, clear differences in the effects of the systemic administration of clozapine and haloperidol on the extracellular concentration of dopamine (DA) and serotonin (5-HT) were found in the nucleus accumbens of freely moving rats. Haloperidol (0.5 mg/kg s.c.) significantly increased DA (ca. 40%) but did not modify 5-HT extracellular concentration, while clozapine (5 mg/kg s.c.) significantly decreased 5-HT (ca. 40%) but did not change DA concentration. Locally infused, clozapine (10(-5) M) significantly increased DA (75%) and reduced 5-HT extracellular concentration (50%). The reduction of 5-HT cannot be explained by a clozapine-induced blockade of DA receptors, because the local infusion (10(-5) M) of the DA D2-like antagonist raclopride and the DA D1-like antagonist SCH 23390 significantly increased DA (ca. 300% and 200%, respectively) but did not modify 5-HT extracellular concentration. Conversely, the DA D2-like agonist quinpirole and the DA D1-like agonist SKF-38393 significantly decreased (ca. 60% in both cases) DA extracellular concentration without affecting that of 5-HT. The present results indicate that clozapine displays a powerful anti-serotoninergic effect by inhibiting 5-HT release in the nucleus accumbens, an effect probably derived from the reduction of firing activity at the dorsal raphe and by local mechanisms that may involve some 5-HT receptor subtype(s).

Animals↗
PubMed1995

Lack of evidence for dopamine autoreceptors in the mediobasal hypothalamus: a microdialysis study in awake rats.

To determine the functional presence of dopamine (DA) autoreceptors on tuberoinfundibular dopamine (TIDA)-ergic neurons in awake rats, a microdialysis probe was implanted into the mediobasal hypothalamus (MBH). In the presence of the re-uptake inhibitor nomifensine, which increased DA levels to 350% of basal values, systemic administration of the non-selective D1/D2 antagonist haloperiol induced an immediate increase in DA and DOPAC levels to 145% of pretreatment values. However, neither local infusion of the selective D2 antagonist sulpiride nor of the D1 antagonist SCH 23390 affected the nomifensine-elevated extracellular DA or DOPAC levels in the MBH. Systemic administration of the D2 antagonist raclopride equally did not affect the nomifensine-elevated DA release in the MBH. Upon basal extracellular DA levels (without nomifensine), local infusion of the D2 agonist (-)N-0437 equally did not affect the DA or DOPAC levels in the MBH. Furthermore, the increase in DA levels induced by haloperidol could not be antagonized by the D1 agonist CY 208-243. Therefore, the present study does not provide support for the concept of functional autoreceptors located on TIDA neurons regulating the release of DA. Possibly, the effect of haloperidol was non-DA-ergic in character.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1983

The effects of DL-tetramisole and rafoxanide on tricarboxylic acid cycle enzymes of Haemonchus contortus, in vitro.

Various enzymes of the tricarboxylic acid cycle (TCA) viz., aconitase (E.C. 4.2.1.3), isocitrate dehydrogenase (E.C. 1.1.1.42), succinate dehydrognease (E.C. 1.3.99.1), fumarate reductase (NADH: fumarate oxido-reductase), fumarase (E.C. 4.2.1.2) and maltate dehydrogenase (E.C. 1.1.1.37) were detected in adult Haemonchus contortus (Nematoda: Trichostrongylidae), in vitro. Low activities of aconitase and isocitrate dehydrogenase suggested that the TCA cycle has a minor function and the pathway of CO2 fixation is the major pathway in the energy metabolism of the parasite. In vitro incubation in Tyrode's solution had no significant effect on TCA cycle enzymes and the worm was able to maintain normal metabolism for 12 h. The effects of D L-tetramisole and rafoxanide on various enzymes of the TCA cycle were studied in adult H. contortus. At 50 micrograms ml-1 varying degrees of inhibition of succinate dehydrogenase and fumarate reductase activities were observed. At the same concentration, the activities of other enzymes remained unaltered.

Animals↗
PubMed1983

The activity of closantel as an equine antiparasitic agent.

Eighteen pony foals were experimentally infected with 500 third stage larvae of Strongylus vulgaris at 2 weeks, and at 2, 4, 6 and 8 months after birth. For the duration of the study, all foals were kept in the same pasture with their mothers to allow natural infection with other parasites by exposure to a contaminated environment. Twelve of the foals were utilized in groups of 3 and treated orally five times at two month intervals starting at one month of age with closantel at doses of 5, 10, 20 or 40 mg kg-1. Ten months after birth the foals were necropsied to determine the parasitic burdens in the gastrointestinal tracts and the cranial mesenteric arteries. The results indicate a high antiparasitic activity of closantel against larval stages of Gasterophilus intestinalis and S. vulgaris, as well as against adult S. vulgaris, S. edentatus, Anoplocephala perfoliata and Triodontophorus spp., when used at doses of 20 or 40 mg kg-1.

Animals↗
PubMed1985

Enzymes of isolated brush border membrane of Cotugnia digonopora, and their insensitivity to anthelmintics in vitro.

Purified brush border membrane of Cotugnia digonopora showed the presence of a number of phosphohydrolases. Among these, alkaline phosphatase was extremely active. Other enzymes such as glucose-6-phosphatase, fructose-1,6-diphosphatase, cAMP-phosphodiesterase, 5'-nucleotidase and adenosine-triphosphatase were also active. Observations were made on the activities of various ATPases; whereas the enzyme was activated by Ca++ and Mg++ in an additive manner, its sensitivity to ouabain was negligible. Furthermore, in the presence of EDTA the enzyme activity was quite significant. The treatment of isolated brush border membrane with mebendazole, niclosamide and praziquantel in vitro did not alter the activity of these enzymes. However, treatment of intact worms drastically affected the integrity of the membrane.

3',5'-Cyclic-AMP Phosphodiesterases↗
PubMed1986

The use of injectable rafoxanide against natural ovine nasal myiasis.

Rafoxanide (Flukanide), 7.5 mg kg-1 b.w. was administered to a group of 17 sheep naturally infected with Oestrus ovis larvae. A similar untreated control group was simultaneously observed for changes in clinical signs and body weights. Three animals from each group were slaughtered and examined for the presence of larval instars of O. ovis. While no larvae were recovered from the treated group, a total of 26 larvae, predominantly first and third instars, were recovered from nasal sinuses of the untreated group. There was clinical recovery and additional weight gain (+3.52 kg) after 2 months in the treated animals and a noticeable clinical deterioration of the untreated animals. The effect of the drug lasted for greater than 25 days.

Animals↗
PubMed1984

Substrates respired by mitochondrial fractions of two isolates of the nematode Aphelenchus avenae and the effects of electron transport inhibitors.

Electron transport has been assayed and compared in two isolates (M and F) of the free-living (model) nematode Aphelenchus avenae. Of the substrates tested only alpha-glycerophosphate and succinate were utilised to any significant extent by both isolates. Comparative data on respiratory rates, respiratory control ratios and ADP:O ratios for various substrates are given. Succinate oxidation by isolate-F mitochondria was ca 80-90% sensitive to antimycin A while that of isolate M was almost completely refractory to antimycin A. The response to other electron transport inhibitors suggests the operation of (a) azide/cyanide sensitive, (b) azide/salicylhydroxamic acid (SHAM) insensitive but carbon monoxide sensitive and (c) SHAM-sensitive terminal oxidases to varying degrees in the mitochondria of these two isolates of A. avenae.

Animals↗
PubMed1994

Effects of selective dopamine receptor compounds on single, spontaneously-active neostriatal neurons.

1. The effects of selective dopamine receptor compounds on the spontaneous activity of single neostriatal neurons were examined extracellularly. 2. Intravenous administration of quinpirole, the D2 agonist, elicited a dose-dependent depression in discharge rate. 3. Quinpirole-evoked depression was reversed by the D2 antagonist eticlopride, but not the D1 antagonist SCH 23390. 4. The partial D1 agonist, SKF 38393 induced depression and excitation in equal proportion. 5. A dose of 0.25 mg/kg SCH 23390 blocked SKF 38393-induced depression but not excitation. 6. SKF 38393-induced excitation was antagonized by eticlopride and in some cases by a higher dose of SCH 23390.

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗
PubMed1989

Localization of striatal dopamine receptor function by central injection of an irreversible receptor antagonist.

The stereotypic head-down sniffing response to systemically administered apomorphine (0.65 mumol/kg) was assessed in rats 48 h after the bilateral injection of 0.2-0.5 microliters of the irreversible receptor antagonist N-ethoxycarbonyl-2-ethoxy-1,2-dihydroquinoline (60 micrograms/microliters) into the caudate-putamen and nucleus accumbens. This response was significantly attenuated in animals that had received injections of N-ethoxycarbonyl-2-ethoxy-1,2-dihydroquinoline into the anterior/ventral part of the caudate-putamen but not in those that received injections into regions more dorsal/posterior. Animals were killed after apomorphine challenge and the region of dopamine D1 or D2 receptor reduction due to N-ethoxycarbonyl-2-ethoxy-1,2-dihydroquinoline mapped and quantified. This analysis revealed that the dopamine receptors involved in the apomorphine-induced stereotyped head-down sniffing response were located in a discrete region of the ventrolateral caudate-putamen and the dorsolateral nucleus accumbens. Animals that were pretreated with the selective dopamine D2 receptor antagonist raclopride (0 20 mumol/kg, i.p.) 20 min prior to central injection of N-ethoxycarbonyl-2-ethoxy-1,2-dihydroquinoline into this area showed a dose-dependent protection of the stereotyped sniffing response to systemic apomorphine 48 h later. This combination of techniques constitutes a novel way to investigate striatal function and the results obtained support the concept of a functional subdivision of both the caudate-putamen and the nucleus accumbens.

Animals↗
PubMed1990

The role of D1 and D2 dopamine receptors in oral stereotypy induced by dopaminergic stimulation of the ventrolateral striatum.

Microinjection of amphetamine into the ventrolateral region of the striatum results in compulsive and intense oral stereotypies in the rat. Although these stereotyped behaviors are known to be a direct result of excessive stimulation of the striatal dopamine neurons, the relative roles of the D1 and D2 receptors in oral stereotypies are not clearly understood. It is reported here that microinjection of the selective D1 agonist, SKF 38393 (0, 0.3, 3.0, 30.0 micrograms in 0.5 microliters vehicle) into the ventrolateral striatum resulted in no observable changes in behavior during the 30-min test period. However, it was observed that intense self-biting emerged 3-4 h following injection. Examination of histology from these animals revealed extensive tissue damage and the delayed onset of biting was hypothesized to result from a neurotoxic effect of SKF 38393. Infusion of quinpirole (0, 0.3, 3.0, 30.0 micrograms in 0.5 microliter vehicle), a selective D2 agonist, resulted in a dose-dependent increase in orofacial behaviors such as licking, wood-chip eating, head-down sniffing and mouth movements. Intense oral stereotypies such as biting or gnawing were not observed following treatment with quinpirole. Infusion of the mixed agonist dopamine (0, 2.0, 10.0, 20.0 micrograms in 0.5 microliter vehicle) into the ventrolateral striatum was found to elicit intense oral stereotypy. This behavior consisted almost exclusively of self-biting similar to that observed following amphetamine microinjection into this region. Haloperidol, when given as either a systemic (0.2 mg/kg) or intra-ventrolateral striatum (2.5 micrograms/0.5 microliter) pretreatment, effectively blocked oral stereotypies induced by amphetamine microinjection into the ventrolateral striatum. Pretreatment with either the D1 antagonist SCH 23390 (0, 0.01, 0.1 mg/kg, i.p.) or the D2 antagonist raclopride (0, 0.05, 0.50, 1.0 mg/kg, i.p.) antagonized amphetamine-induced oral stereotypy in a dose-dependent manner. These findings demonstrate that within the striatal site specifically implicated in oral behavior, concurrent stimulation of both receptor subtypes is necessary for the expression of intense oral stereotypies.

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗
PubMed1991

Distribution of dopaminergic receptors in the primate cerebral cortex: quantitative autoradiographic analysis using [3H]raclopride, [3H]spiperone and [3H]SCH23390.

A widespread distribution of dopamine D1 receptors in the neocortex is well recognized. However, the presence of dopamine D2 receptors in this structure has only recently been established [Martres et al. (1985) Eur. J. Pharmac. 118, 211-219; Lidow et al. (1989) Proc. natn. Acad. Sci. U.S.A. 86, 6412-6416]. In the present paper, a highly specific antagonist, [3H]raclopride, was used for autoradiographic determination of the distribution of D2 receptors in 12 cytoarchitectonic areas of the frontal, parietal, and occipital lobes of the rhesus monkey. A low density of D2-specific [3H]raclopride binding (1.5-4.0 fmol/mg tissue) was detected in all layers of all cortical areas studied. Throughout the entire cortex, the highest density of binding was consistently found in layer V. This is a unique distribution not observed so far for any other neurotransmitter receptor subtype in monkey cerebral cortex, including D1 receptor. In addition, a comparison was made of the distribution of [3H]raclopride and [3H]spiperone, which has been commonly used in previous attempts to label cortical D2 receptors. We found marked differences in the distribution of these two radioligands. In the prefrontal cortex, the pattern of [3H]spiperone binding in the presence of ketanserin resembled the combined distribution of 5-HT1C serotoninergic and alpha 2-adrenergic sites as well as D2 receptors. Thus, [3H]raclopride provides a better estimation of the D2 receptor distribution than does [3H]spiperone. The distribution of D2-specific binding of [3H]raclopride was also compared with the D1-specific binding of [3H]SCH23390 in the presence of mianserin to block labeling to 5-HT2 and 5-HT1C sites. The density of D1-specific [3H]SCH23390 binding was 10-20 times higher than that of D2-specific [3H]raclopride binding throughout the cortex. The densities of both [3H]raclopride and [3H]SCH23390 binding sites display a rostral-caudal gradient with the highest concentrations in prefrontal and the lowest concentrations in the occipital cortex. However, the binding sites of these two ligands had different laminar distributions in all areas examined. In contrast to preferential [3H]raclopride binding in layer V, a bilaminar pattern of [3H]SCH23390 labeling was observed in most cytoarchitectonic areas, with the highest concentrations in supragranular layers I, II and IIIa and infragranular layers V and VI. Whereas [3H]raclopride binding was similar in all cytoarchitectonic areas, [3H]SCH23390 exhibited some region-specific variations in the primary visual and motor cortex. The different regional and laminar distributions of D1 and D2 dopaminergic receptors indicates that they may subserve different aspects of dopamine function in the cerebral cortex.

Animals↗
PubMed1991

Positive and negative interactions in the behavioural expression of D1 and D2 receptor stimulation in a model of Parkinsonism: role of priming.

Previous exposure to a dopaminergic agonist (priming) strongly potentiates contralateral turning behaviour in response to D1 and D2 agonists in unilaterally 6-hydroxydopamine-lesioned rats. In order to study the influence of priming on the behavioural interaction of D1 and D2 receptors, we examined the effect of selective D1 and D2 receptor blockade on the contralateral turning induced by the mixed D2/D2 agonist apomorphine in drug-naive and primed 6-hydroxydopamine-lesioned rats. In drug-naive rats, apomorphine induced a dose-related, apparently monophasic rotation curve. Administration of selective D1 (SCH 23390) or D2 (raclopride) antagonists abolished the contralateral turning induced by 0.1 mg/kg of apomorphine and partially inhibited that induced by 0.5 mg/kg. In primed rats low doses of apomorphine (0.05 mg/kg) induced an apparently monophasic contralateral turning which was reduced by D1 receptor blockade and completely abolished by D2 receptor blockade; a higher dose of apomorphine (0.1 mg/kg) instead elicited a biphasic (two-peak) pattern of rotation. After this dose of the agonist, blockade of D1 or D2 receptors abolished the second peak of rotation but, while D1 blockade reduced the total number of turns, D2 blockade failed to do so. Quantitative analysis of the interaction between D1 and D2 receptors in the overall turning effect, as well as in the time-course of turning behaviour, indicates that D1 and D2 receptors interact not only positively but also negatively. After higher doses of apomorphine, both negative and positive interactions take place sequentially during the time-course of apomorphine action and provide a clue for explaining the two-peak pattern of rotation observed after apomorphine in rats previously exposed to the drug.

Animals↗
PubMed1991

Dopaminergic D1 and D2 receptor antagonists decrease prosomatostatin mRNA expression in rat striatum.

The effect of acute dopamine receptor antagonist treatment on cellular prosomatostatin mRNA expression was investigated in the adult rat striatum using the technique of non-radioactive in situ hybridization. Adult female Wistar rats were given a single intraperitoneal injection of either raclopride (D2 antagonist), SCH 23390 (D1 antagonist) or the D1 (S) enantiomer SCH 23388. Animals were killed either 1, 3 or 9 h following the single i.p. injection and their brains rapidly removed. Striatal sections were then processed for in situ hybridization using an alkaline phosphatase-labelled oligonucleotide probe complementary to a portion of the rat somatostatin cDNA. Blockade of dopamine D1 and D2 receptors resulted in a significant decrease in the cellular content of prosomatostatin mRNA. However, no change in the number of prosomatostatin mRNA containing striatal cells was observed following any of the treatments at any time point. These findings demonstrate that the cellular content of prosomatostatin mRNA in the adult rat striatum is influenced by selective dopamine D1 and D2 receptor antagonists. Further, these findings are consistent with a functional interaction between dopamine and somatostatin in the rat striatum.

Animals↗
PubMed1991

Chronic eticlopride and dopamine denervation induce equal nonadditive increases in striatal D2 receptor density: autoradiographic evidence against the dual mechanism hypothesis.

In an attempt to resolve experimental discrepancies regarding the mode of action of D2 receptor regulation following denervation or chronic receptor blockade, rats with extensive unilateral destruction of the mesotelencephalic dopaminergic projections induced by intracerebral 6-hydroxydopamine were injected daily for 21 days with either saline or the potent, selective D2 antagonist eticlopride (0.5 mg/kg, i.p.). Four days after the last injection of eticlopride or saline, rats were killed, and brain sections through the caudate-putamen and nucleus accumbens septi were incubated with [3H]spiroperidol or (R)-(+)-8-chloro-2,3,4,5-tetrahydro-3-methyl-5- phenyl-1H-3-benzazepin-7-ol ([3H]SCH 23390) to assay D2 and D1 receptors, respectively. Autoradiographic analysis revealed that chronic eticlopride treatment increased the density of D2 sites in the intact hemisphere for all regions examined without further augmenting the already increased density of D2 receptors seen in the dopamine-denervated hemisphere. D2 receptor density was independent of functional sensitivity as evidenced by the fact that rats treated chronically with eticlopride rotated contralateral to the 6-hydroxydopamine lesion following systemic administration of the selective D2 agonist quinpirole during the neuroleptic wash-out period, despite the fact that D2 receptor binding was not significantly different in the left and right hemispheres of these subjects. D1 receptor density was not affected by eticlopride treatment but was significantly reduced reduced in the dopamine-denervated hemisphere. [3H]Mazindol labeling of high-affinity DA uptake sites indicated that the extent of dopamine denervation was greater than 97% in both saline- and eticlopride-treated rats.(ABSTRACT TRUNCATED AT 250 WORDS)

Analysis of Variance↗