Biomedical subjects

L W Zhou

Publications and source records attributed to L W Zhou.

At least 19 recordsLinked to original sources

PubMed2006

Structure of electrorheological fluids under an electric field and a shear flow: experiment and computer simulation.

It is known that macroscopic properties of colloidal suspensions are often determined by the microstructure of the particles in the suspensions, depending on the interparticle, Brownian, and hydrodynamic (if any) forces. We take electrorheological (ER) fluids as an example. By using a computer simulation and an experimental approach, we investigate the structure of ER fluids subjected to both an electric field and a shear flow. The microstructure evolution from random structure, to chains, and then to stable lamellar patterns, observed in the experiments, agrees very well with that obtained in the simulations. It is shown that the formation of such lamellar patterns originates from the difference between the dipole moment induced in the particles suspended in the ER fluids without shear and the one with shear. The results on the relaxation process of structural formation and the internal structure of layers are also presented. Thus, it seems possible to achieve various structures and hence desired macroscopic properties of colloidal suspensions by adjusting external fields and, simultaneously, a shear flow.

Computer Simulation↗

PubMed2006

Effect of low power laser irradiation on disconnecting the membrane-attached hemoglobin from erythrocyte membrane.

In our previous study we found that low power laser irradiation improved the erythrocyte deformability, but the mechanism is unclear. The membrane-attached hemoglobin (Hbm) may be one of the determining factors for the erythrocyte deformability. We report here for the first time, that laser irradiation can reduce the Hbm contents in pig's erythrocytes, providing the explanation for the improvement of erythrocyte deformability. The decrease of the Hbm was proportional to the irradiation dose, but the relative change of Hbm was saturated around 35%. The 532 nm laser was more efficient at lowering Hbm than the 632.8 nm laser, consistent with the absorption spectrum of Hbm.

Animals↗

PubMed2004

A comparative study of 632.8 and 532 nm laser irradiation on some rheological factors in human blood in vitro.

The effects of laser irradiation with 632.8 and 532 nm on rheological properties of blood were comparatively studied in vitro. Under the irradiation condition of 30 mW, laser irradiation of blood samples using a spot diameter of 5 mm with each laser, showed promising results in the modulation of hemorheological properties. When blood samples from patients with abnormally high values of erythrocyte sedimentation rate (ESR) were irradiated, the values of ESR were lowered statistically by either of the 632.8 or 532 nm lasers. The laser irradiation reduced blood viscosities at different shear rates (10-110 S(-1)) for the hyper-viscosity blood samples. Laser irradiation increased the electrophoretic mobility (EPM) of erythrocytes when the values of the sample's EPM were abnormally slow. The erythrocyte deformability was enhanced by laser irradiation when the deformability of the sample from the patients was originally poor. For verifying the improvement of laser irradiation on erythrocyte deformability, the typical erythrocyte samples with poor deformability were produced by the pre-treatment of the erythrocytes with Ca(2+). The deformability of these erythrocyte samples was also improved after laser irradiation. These results suggest that membrane-bound hemoglobin (Hbm) might be the initial site of the interaction, since Hbm is the main cause of poor deformability when erythrocytes were treated with Ca(2+). In all experiments including ESR, blood viscosity, EPM and erythrocyte deformability, the 532 nm laser demonstrated more efficient effects on modulating rheological properties than 632.8 nm laser. This wavelength effect is consistent with the absorption spectrum of hemoglobin, reflecting that hemoglobin may be one of the action targets under laser irradiation.

Blood↗

PubMed1999

Antisense RNA gene therapy for studying and modulating biological processes.

Agents that produce their effects through an antisense mechanism offer the possibility of developing highly specific alternatives to traditional pharmacological antagonists, thereby providing a novel class of therapeutic agents, ones which act at the level of gene expression. Among the antisense compounds, antisense RNA produced intracellularly by an expression vector has been used extensively in the past several years. This review considers the advantages of the antisense RNA approach over the use of antisense oligodeoxynucleotides, the different means by which one may deliver and produce antisense RNA inside cells, and the experimental criteria one should use to ascertain whether the antisense RNA is acting through a true antisense mechanism. Its major emphasis is on exploring the potential therapeutic use of antisense RNA in several areas of medicine. For example, in the field of oncology antisense RNA has been used to inhibit several different target proteins, such as growth factors, growth factor receptors, proteins responsible for the invasive potential of tumor cells and proteins directly involved in cell cycle progression. In particular, a detailed discussion is presented on the possibility of selectively inhibiting the growth of tumor cells by using antisense RNA expression vectors directed to the individual calmodulin transcripts. Detailed consideration is also provided on the development and potential therapeutic applications of antisense RNA vectors targeted to the D2 dopamine receptor subtype. Studies are also summarized in which antisense RNA has been used to develop more effective therapies for infections with certain viruses such as the human immunodeficiency virus and the virus of hepatitis B, and data are reviewed suggesting new approaches to reduce elevated blood pressure using antisense RNA directed to proteins and receptors from the renin-angiotensin system. Finally, we outline some of the problems which the studies so far have yielded and some outstanding questions which remain to be answered in order to develop further antisense RNA vectors as therapeutic agents.

Animals↗

PubMed1999

Cytosolic-Ca2+ and coxsackievirus B3-induced apoptosis in cultured cardiomyocytes of rats.

AIM: To explore the role of cytosolic free calcium ([Ca2+]i) in apoptosis induced by coxsackievirus B3 (CVB3) in cultured cardiomyocytes of rats. METHODS: Primary cultured cardiomyocyte was prepared from Wistar rats ages 2-3 d. The apoptosis in cardiomyocyte was determined by terminated deoxynucleotide transferase directed d-UTP nick and end labeling (TUNEL) method, and the apoptosis was observed under a transmission electron microscope. [Ca2+]i in single cardiomyocyte loaded with Fluo 3-AM was measured by confocal microsorope. RESULTS: (1) The concentration of CVB3 in the medium reached the peak at 24 h after CVB3 infection. (2) The apoptotic cells were not found in CVB3-infected cardiomyocyte in first 10 h, but amounted to 5% at 17 h, 60% at 24 h, and 90% at 36 h. (3) The peak value of [Ca2+]i elevation reached at 17 h after CVB3 infection (P < 0.01). (4) The characteristics of apoptosis was also seen by transmission electron microscope. CONCLUSION: CVB3 induced the apoptosis in cultured cardiomyocyte, and [Ca2+]i mobilization was involved in the signal transduction process in apoptosis cells, and played an important role especially in the early stage of apoptosis induced by CVB3.

Animals↗

PubMed1998

Isolation and characterization of a new gene, sre, which encodes a GATA-type regulatory protein that controls iron transport in Neurospora crassa.

Multiple GATA factors - regulatory proteins with consensus zinc finger motifs that bind to DNA elements containing a GATA core sequence - exist in the filamentous fungus Neurospora crassa. One GATA factor, NIT2. controls nitrogen metabolism, whereas two others, WC-1 and WC-2, regulate genes responsive to blue light induction. A gene encoding a new GATA factor, named SRE, was isolated from Neurospora using a PCR-mediated method. Sequence analysis of the new GATA factor gene revealed an ORF specifying 587 amino acids, which is interrupted by two small introns. Unlike all previously known Neurospora GATA factors, which possess a single zinc-finger DNA-binding motif, SRE contains two GATA-type zinc fingers. The deduced amino acid sequence of SRE shows significant similarity to URBSI of Ustilago and SREP of Penicillium. A loss-of-function mutation was created by the RIP procedure. Analysis of sre+ and sre- strains revealed that SRE acts as a negative regulator of iron uptake in Neurospora by controlling the synthesis of siderophores. Siderophore biosynthesis is repressed by high iron concentrations in the wild-type strain but not in sre- mutant cells. The sre promoter contains a number of GATA sequences; however, expression of sre mRNA occurs in a constitutive fashion and is not regulated by the concentration of iron available to the cells.

Amino Acid Sequence↗

PubMed1998

[Chemical constituents of Phyllanthus urinaria L. and its antiviral activity against hepatitis B virus].

Studies on the chemical constituents of Phyllanthus urinaria and its antiviral activity against hepatitis B virus were completed. Eleven compounds have been isolated. Two of them are new compounds methyl ester dehydrochebulic acid and methyl brevifolin carboxylate. Antiviral experiments on HBsAg in vitro and liver damage caused by CCl4 have shown that. Phyllanthus urinaria possesses antiviral activities against HBV.

Animals↗

PubMed1998

D2 dopamine antisense RNA expression vector, unlike haloperidol, produces long-term inhibition of D2 dopamine-mediated behaviors without causing Up-regulation of D2 dopamine receptors.

Long-term inhibition of D2 dopamine receptors using classic D2 dopamine receptor antagonists such as haloperidol often causes a compensatory up-regulation of the D2 dopamine receptors. We investigated whether the long-term inhibition of D2 dopamine receptors using an eukaryotic expression vector housing a cDNA sequence encoding an antisense RNA directed to the D2 dopamine receptor transcript (D2 antisense vector) would also produce up-regulation of the D2 receptors. Single, bilateral injections of the D2 antisense vector into the corpora striata of mice inhibited the stereotypy induced by acute challenge injections with the D2/D3 dopamine receptor agonist quinpirole but did not inhibit the grooming induced by acute challenge injections with the D1 agonist SKF 38393. Similar treatment with the D2 antisense vector produced a long-term (>1 month) cataleptic response without producing tolerance to challenge injections with haloperidol. By contrast, catalepsy induced by a single injection of haloperidol lasted only approximately 2 days, and tolerance developed to its effects after long-term treatment. Repeated treatment of mice with haloperidol resulted in an inhibition of apomorphine-induced climbing behavior throughout the time of treatment with haloperidol, but the climbing behavior markedly increased to levels significantly higher than that of the control mice immediately after withdrawal from haloperidol treatment. This increased climbing was accompanied by increased levels of D2 dopamine receptors in the striatum. By contrast, single, bilateral intrastriatal injections of the D2 antisense vector significantly inhibited apomorphine-induced climbing for approximately 30 days but failed to increase the climbing behavior or the levels of D2 dopamine receptors in striatum over those of the control values. These results suggest that a single injection of a D2 antisense RNA expression vector into mouse striatum produces specific, long-term inhibition of D2 dopamine receptor behaviors without causing a compensatory increase in the levels or function of D2 dopamine receptors.

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

PubMed1997

Antisense strategies in dopamine receptor pharmacology.

Recent advances in molecular biology have provided pharmacologists the opportunity of developing an entirely new type of agent for studying and treating a variety of biological disorders. These agents, termed antisense oligodeoxynucleotides, have as their target the messenger RNAs encoding specific proteins. They act by binding to selected portions of these mRNAs through complimentary interactions and thereby prevent the synthesis of these proteins. These novel pharmacological tools have the promise of being easier to design and being more selective and predictable in their actions. In addition, insofar as agents targeted to receptors for neurotransmitters are concerned, unlike the classical pharmacological agents, these new compounds may not lead to the upregulation of the very receptors the drugs are designed to inhibit. The present review summarizes briefly studies on the effect of oligodeoxynucleotides antisense to the mRNAs encoding the various subtypes of the dopamine receptor. The studies show that oligodeoxynucleotides antisense to the D2 dopamine receptor when intracerebroventricularly into brains of rodents are rapidly taken up into the brain tissue, distributed to brain cells, and produce effects characteristic of highly selective D2 dopamine antagonists. The compounds also produced specific reductions in the levels of D2 dopamine receptor mRNA and D2 dopamine receptors. Similarly, injecting an antisense oligodeoxynucleotide targeted to the D1 dopamine receptor mRNA produces effects characteristic of D1 dopamine receptor antagonists. Other studies using these agents has produced evidence that there is a small pool of receptors that turn over very rapidly and which constitute the functional pool of these receptors. The evidence suggests further that antisense oligodeoxynucleotides inhibit the synthesis of this small functional pool of dopamine receptors, thereby providing an explanation of why there is often a discordance between changes in dopaminergic function and changes in the levels of dopamine receptors. Studies of antisense oligodeoxynucleotides targeted to the other subtypes of dopamine receptor may help reveal the biological roles that these and other newly discovered subtypes of neurotransmitter receptors have. They may also provide an entirely new and potentially more selective therapeutic regimen for altering the functions of these receptors.

Animals↗

PubMed1997

Expression of a D2 dopamine receptor antisense RNA in brain inhibits D2-mediated behaviors.

Drugs currently used to treat disorders of dopamine-mediated behaviors in the central nervous system are non-selective in that they interact not only with more than one isoform of dopamine receptor but also with receptors for other neurotransmitters. A new strategy to inhibit the actions of individual dopamine receptor subtypes is to inhibit the synthesis of the receptors through the use of oligonucleotides antisense to the transcripts encoding the different receptors. Earlier studies showed that oligodeoxynucleotides antisense to the D1 or D2 dopamine receptor messenger RNAs specifically inhibited the biological actions mediated by these individual isoforms of the dopamine receptor. However, these actions were relatively short-lasting. To determine whether one can achieve long-lasting inhibition of dopamine responses, while still taking advantage of the highly selective nature of an antisense strategy, an expression vector was employed that generates antisense RNA to the transcript encoding the D2 dopamine receptor. A single intrastriatal injection of this vector generated an antisense RNA to the D2 dopamine receptor, selectively reduced the levels of D2 dopamine receptors, and caused selective, long-term inhibition of behaviors mediated by D2 dopamine agonists. Such an antisense RNA strategy may find use in studying the function of dopaminergic receptors and in disorders associated with dopaminergic hyperactivity.

Animals↗

PubMed1996

D2 dopamine receptor antisense increases the activity and mRNA of tyrosine hydroxylase and aromatic L-amino acid decarboxylase in mouse brain.

A D2 dopamine receptor antisense oligodeoxynucleotide was administered intracerebrovetricularly to mice twice on the first day and then once daily for 2 days. The animals were killed 2 h after the last injection, and tyrosine hydroxylase and aromatic L-amino acid decarboxylase activities assayed in the corpus striatum, olfactory tubercle and frontal cortex. Tyrosine hydroxylase activity increased in corpus striatum but not in the olfactory tubercle or in the frontal cortex, while the activity of aromatic L-amino acid decarboxylase increased in all three brain regions. The treatment with the antisense oligomer also elevated the mRNA levels for the two enzymes in the midbrain. In contrast, repeated injection of a vehicle or a random oligomer was without effect on enzyme activity or mRNA D2 antisense oligodeoxynucleotides appear to be selective tools to investigate the role of D2 dopamine receptors in brain.

Animals↗

PubMed1996

Uptake and distribution of fluorescein-labeled D2 dopamine receptor antisense oligodeoxynucleotide in mouse brain.

To determine the uptake and distribution of oligodeoxynucleotides in brain, a 20-mer phosphorothioated oligodeoxynucleotide complementary to a portion of the D2 dopamine receptor mRNA was fluorescently labeled with fluorescein isothiocyanate (FITC) and injected into the lateral cerebral ventricles of mice. At various survival times after the injection, the brains were removed, fixed, sectioned, and viewed under a fluorescent microscope. The results showed that the oligodeoxynucleotide was rapidly taken up into the brain. Initially the label was relatively diffusely spread throughout the interstitial spaces of the brain, then became redistributed to the cellular compartments. The signal extended from those forebrain nuclei located immediately in contact with the ventricles, such as the corpus striatum, septum, and hippocampus, to areas further removed from the ventricles, such as the cerebral cortex, nucleus accumbens, and substantia nigra. When the FITC-labeled D2 antisense oligodeoxynucleotide was given once daily for 4 d, the signal intensity seen 24 h after the last injection appeared to be of greater intensity overall compared to that seen after a single injection. At early time-points the oligodeoxynucleotide signals appeared to be punctuated and were found in cell bodies as well as in proximal dendritic processes. However, not all cells were equally labeled, suggesting an uneven uptake and accumulation of the D2 antisense into the various cell types. At later time-points the fluorescent signal appeared granular; at these times the injected material was largely degraded. These studies show that a D2 dopamine receptor antisense oligodeoxynucleotide is rapidly taken up from cerebral ventricles into brain, becomes widely distributed throughout the brain tissue to areas far removed from direct contact with the ventricles, and appears to accumulate to a different extent in the various brain areas and cell types.

Animals↗

PubMed1996

Intrastriatal administration of an oligodeoxynucleotide antisense to the D2 dopamine receptor mRNA inhibits D2 dopamine receptor-mediated behavior and D2 dopamine receptors in normal mice and in mice lesioned with 6-hydroxydopamine.

Previous studies have shown that the intracerebroventricular injection of antisense oligodeoxynucleotides targeted to the mRNAs encoding the different subtypes of dopamine receptors inhibited behaviors mediated by these receptors. The present studies were designed to determine whether such antisense oligodeoxynucleotides could produce similar effects when injected into a discrete brain area. A D2 dopamine receptor antisense oligodeoxynucleotide (D2 antisense) was repeatedly injected into one corpus striatum of either normal mice or mice with unilateral lesions of the striatum induced by 6-hydroxydopamine. In the latter, intrastriatal injection of D2 antisense blocked the contralateral rotational behavior induced by the parenteral administration of the D2 dopamine receptor agonist quinpirole. The inhibitory effect of D2 antisense was dose- and time-related and was reversed upon cessation of D2 antisense treatment. This inhibitory effect was also selective in that D2 antisense treatment inhibited the rotational behavior induced by quinpirole but not that induced by the D1 dopamine receptor agonist SKF 38393 or by the muscarinic cholinergic agonist oxotremorine. Following repeated intrastriatal injections of D2 antisense into normal mice, parenteral administration of quinpirole caused rotational behavior ipsilateral to the side in which the D2 antisense was injected. No such rotational behavior was seen when similarly treated mice were challenged with SKF 38393 or oxotremorine. The quinpirole-induced rotational behavior in mice given intrastriatal injections of D2 antisense disappeared upon cessation of D2 antisense treatment. Repeated intrastriatal administration of D2 antisense also caused a significant reduction in the levels of D2, but not D1, dopamine receptors in striatum, as determined by receptor autoradiography. The levels of D2 dopamine receptors returned to normal upon cessation of D2 antisense treatment. Intrastriatal administration of an oligodeoxynucleotide with randomly placed nucleotides failed to alter the rotational response to quinpirole in either 6-hydroxydopamine-lesioned or normal mice and failed to alter the levels of D2 dopamine receptors in striatum. These results show that selective inhibition of behavioral responses mediated by D2 dopamine receptors can be achieved by the direct injection of a D2 antisense oligodeoxynucleotide into a discrete brain area.

Animals↗

PubMed1995

Continuous infusion of clozapine increases mu and delta opioid receptors and proenkephalin mRNA in mouse brain.

The biochemical mechanisms involved in the actions of the atypical antipsychotic clozapine are still unclear. Because elevated levels of enkephalin in certain areas of the central nervous system may be necessary for antipsychotic activity, we have examined the effect of clozapine on certain receptors and mRNA transcripts involved in the opioid peptidergic system. Clozapine was infused continuously into mice for 21 days and the density of mu and delta opioid receptors was measured in the brains by quantitative receptor autoradiography, and the level of proenkephalin mRNA and dopamine D1 and D2 receptor mRNA were measured by in situ hybridization histochemistry. The results showed that continuous infusion of clozapine increased the density of D1 but not D2 receptors. However, it failed to alter the levels of either D1 or D2 dopamine receptor mRNA. By contrast, clozapine increased the density of mu and delta opioid receptors and increased the levels of proenkephalin mRNA. These results indicate that continuous treatment with clozapine increases opioid peptidergic activity in mouse brain and suggest that alteration of peptidergic activity as well as alteration of dopaminergic activity may be involved in its antipsychotic action.

Animals↗

PubMed1995

D2 dopamine receptor antisense oligodeoxynucleotide inhibits the synthesis of a functional pool of D2 dopamine receptors.

In vivo administration of an antisense oligonucleotide targeted toward the D2 dopamine (DA) receptor mRNA (D2 AS) markedly inhibited D2 receptor-mediated behaviors but produced only a relatively small reduction in the levels of D2 DA receptors in mouse striatum. This apparent dissociation between DA receptor-mediated behaviors and the levels of D2 DA receptors was addressed by inhibiting the total number of D2 DA receptors by intraperitoneal administration of the selective, irreversibly acting D2 DA receptor antagonist fluphenazine-N-mustard (FNM) and then determining the effects of D2 AS, administered intracerebroventricularly, on the rate of synthesis of D2 DA receptors and on the recovery of D2 receptor-mediated behaviors. FNM inactivated approximately 90% of D2 DA receptors within 4 hr of treatment, after which the receptors returned to normal levels by approximately 8 days. D2 AS treatment significantly inhibited the rate of recovery of D2 DA receptors in striatum of FNM-treated mice. FNM treatment also produced a number of behavioral alterations, including catalepsy, and the inhibition of stereotypic behavior induced by the D2/D3 DA receptor agonist quinpirole. Both of these behaviors returned to normal within 8 days after FNM treatment. D2 AS treatment delayed the restoration of these FNM-induced behaviors. Thus, it reduced the rate of disappearance of the cataleptic behavior induced by FNM and significantly delayed the restoration of the stereotypic behavior induced by quinpirole. The changes induced by D2 AS on D2 receptor-mediated behaviors were reversed on cessation of D2 AS treatment. A random oligomer given in the same amount and for the same length of time as that of the D2 AS had no significant effects on either D2 DA receptor synthesis or DA receptor-mediated behaviors. These studies demonstrate that in vivo administration of D2 AS decreased the rate of recovery of D2 DA receptors and inhibited the recovery of D2 DA receptor-mediated behaviors after irreversible receptor inactivation and suggest that D2 AS treatment inhibits the synthesis of a functional pool of D2 DA receptors.

Animals↗

PubMed1994

D2 dopamine receptor messenger RNA is altered to a greater extent by blockade of glutamate receptors than by blockade of dopamine receptors.

To study further the molecular mechanisms by which glutamate and dopamine interact to regulate the functions of the basal ganglia, the effects of persistently inhibiting dopamine receptors and glutamate N-methyl-D-aspartate receptors on the density of D1 and D2 dopamine receptors and on the level of their transcripts were examined in mouse brain. To block dopamine receptors, mice were treated with N-ethoxycarbonyl-2-ethoxy-1,2-dihydroquinoline once daily for two and six days, or were treated with fluphenazine-N-mustard once daily for five days. To block N-methyl-D-aspartate receptors, mice were treated with dizocilpine by continuous infusion with osmotic mini-pumps for two and six days. The density of D1 and D2 dopamine receptors was measured by receptor autoradiography, and the level of D1 and D2 dopamine receptor messenger RNA was measured by in situ hybridization histochemistry. The results showed that N-ethoxycarbonyl-2-ethoxy-1,2-dihydroquinoline blocked about 90% of both D1 and D2 dopamine receptors, but had no significant effect on the level of either D1 or D2 dopamine receptor messenger RNA. Fluphenazine-N-mustard, which was as effective as N-ethoxycarbonyl-2-ethoxy-1,2-dihydroquinoline in blocking D2 dopamine receptors but had little effect on D1 dopamine receptors, also had no significant effect on the level of D1 and D2 dopamine receptor messenger RNAs. By contrast, continuously infusing dizocilpine significantly decreased the levels of D2 dopamine receptor messenger RNA in striatum, nucleus accumbens and olfactory tubercle. Dizocilpine also caused small decreases in the density of D2 dopamine receptors, but only in posterior striatum was this decrease statistically significant. Dizocilpine slightly and transiently decreased the levels of D1 dopamine receptor messenger RNA in striatum but had no significant effect on the density of D1 dopamine receptors in any region examined. This study demonstrates that persistent blockade of D1 and D2 dopamine receptors has relatively little effect on the levels of D1 and D2 dopamine receptor messenger RNA, but that blockade of N-methyl-D-aspartate receptors produces a rapid and profound decrease in the levels of D2 dopamine receptor messenger RNA and a smaller decrease in the density of D2 dopamine receptors. These results suggest that N-methyl-D-aspartate receptors play an important role in the expression of D2 dopamine receptors in basal ganglia.

Animals↗

PubMed1994

Oligodeoxynucleotide antisense to the D1 dopamine receptor mRNA inhibits D1 dopamine receptor-mediated behaviors in normal mice and in mice lesioned with 6-hydroxydopamine.

The effects of intracerebroventricular (i.c.v.) administration of a 20-mer phosphorothioate oligodeoxynucleotide antisense to the D1 dopamine receptor mRNA (D1 antisense) on D1 dopamine receptor-mediated behaviors were studied in normal mice and in mice with unilateral 6-hydroxydopamine-induced lesions of corpus striatum. Treating mice with D1 antisense inhibited grooming behavior induced by the D1 dopamine receptor agonist SKF 38393 [1-phenyl-2,3,4,5-tetrahydro-1H-3 benzazepine-7,8-diol hydrochloride], the reduction in grooming being related to the amount and length of time D1 antisense was given, with significant reductions in grooming behavior observed within 2 days of repeated injections of D1 antisense. Administering D1 antisense also inhibited rotational behavior induced by SKF 38393 in mice with unilateral 6-hydroxydopamine-induced lesions of corpus striatum. This inhibitory effect on rotational behavior could not be overcome by increasing the dose of SKF 38393. Recovery from inhibition of both grooming and rotational behaviors occurred after cessation of D1 antisense treatment. An oligomer with a similar composition of bases but placed in a random sequence failed to alter grooming or rotational behaviors induced by SKF 38393. In contrast to its effects on D1-mediated behaviors, treatment with D1 antisense had no significant inhibitory effect on stereotyped behavior induced by the D2 dopamine receptor agonist quinpirole [trans-(-)-4,4a,5,6,7,8,8a,9-octahydro-5-propyl-1H(or 2H)-pyrazolo- (3,4g)-quinoline dihydrochloride] in normal mice and produced no significant inhibition of rotational behavior induced either by quinpirole or by the muscarinic cholinergic agonist oxotremorine in 6-hydroxydopamine-lesioned mice.(ABSTRACT TRUNCATED AT 250 WORDS)

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

PubMed1994

In vivo administration of an oligodeoxynucleotide antisense to the D2 dopamine receptor messenger RNA inhibits D2 dopamine receptor-mediated behavior and the expression of D2 dopamine receptors in mouse striatum.

A 20-mer phosphorothioate oligodeoxynucleotide (D2 antisense) to the D2 antisense dopamine receptor messenger RNA (mRNA) was administered i.c.v. to mice with unilateral 6-hydroxydopamine lesions of the corpus striatum. The mice were then challenged with acute injections of various agents that cause contralateral rotational behavior, and the levels of D1 and D2 dopamine receptors and their respective mRNAs were determined in the corpus striatum. Administering the D2 antisense inhibited rotations induced by the D2 dopamine receptor agonists quinpirole and N-propyl-N-2-thienylethylamine-5-hydroxytetralin but did not block rotations induced by the D1 dopamine receptor agonist 1-phenyl-2,3,4,5-tetrahydro-1H-3 benzazepine-7,8-diol HCl or by the muscarinic cholinergic receptor agonist oxotremorine. The reduction in quinpirole-induced rotational behavior was related to the amount and length of time the D2 antisense was given. Significant reductions in behavior were seen within 1 day of repeated injections of D2 antisense, and almost complete inhibition was seen after 6 days of treatment. Recovery from inhibition occurred by 2 days after cessation of antisense treatment. Repeated treatment with D2 antisense significantly reduced the levels of D2 dopamine receptors and D2 dopamine receptor mRNA, but not the levels of D1 receptors or D1 mRNA, in the dorsolateral area of the lesioned striatum. Treatment with an oligodeoxynucleotide with randomly placed nucleotides did not inhibit quinpirole-induced rotations or alter D2 dopamine receptors or D2 dopamine receptor mRNA in either area of striatum.(ABSTRACT TRUNCATED AT 250 WORDS)

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