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Biomedical subjects

B Weiss

Publications and source records attributed to B Weiss.

At least 145 records · Page 8Linked to original sources
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↗
PubMed1993

Irreversible blockade of D2 dopamine receptors by fluphenazine-N-mustard increases glutamic acid decarboxylase mRNA in rat striatum.

The influence of dopaminergic activity on the function of GABAergic neurons in striatum was examined by administering rats the irreversible D2 dopamine receptor antagonist, fluphenazine-N-mustard (FNM), and determining the level of glutamic acid decarboxylase (GAD) mRNA in striatum. Rats were given either an acute single injection or chronic daily injections of FNM (20 mumol/kg, i.p.) for 6 days. The level of GAD mRNA in striatum was determined by in situ hybridization histochemistry. The results showed that acute treatment with FNM failed to significantly change striatal GAD mRNA. However, chronic FNM treatment significantly increased in the level of striatal GAD mRNA. These results demonstrate that irreversible blockade of D2 dopamine receptors increases the expression of GAD mRNA in rat striatum.

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗
PubMed1993

Differential regulation of release of acetylcholine in the striatum in mice following continuous exposure to selective D1 and D2 dopaminergic agonists.

The effect of continuously infusing the selective D1 and D2 dopamine receptor agonists, SKF 38393 and quinpirole, on the release of [3H]acetylcholine from prelabeled striatal slices was investigated. These biochemical parameters were correlated with the behavioral effects of these agonists. Acute injections of SKF 38393 or quinpirole did not affect either K(+)-stimulated or spontaneous release of [3H]acetylcholine. Chronic exposure to quinpirole reduced the K(+)-evoked release of [3H]acetylcholine by 25.7%; long-term treatment with SKF 38393 did not alter the release of [3H]acetylcholine, induced by K+ stimulation. Added in vitro, SKF 38393 increased the release of [3H]acetylcholine from striatal slices. The effect of the D1 dopamine receptor agonist, SKF 38393 was reduced after 7-days of infusion of SKF 38393 but was enhanced by 7-days of infusion of quinpirole. Activation of D2 dopamine receptors with quinpirole or of muscarinic receptors with carbachol induced an inhibition of release of [3H]acetylcholine. Chronic treatment with quinpirole diminished the response to the in vitro addition of quinpirole. The ability of carbachol to inhibit release of acetylcholine was not altered by continuous treatment with either SKF 38393 or quinpirole. Continuous infusion of SKF 38393 produced an initial grooming behavior; this behavior disappeared by 2 hr and remained absent during the 7 days of infusion of SKF 38393. Similarly, continuous administration of quinpirole produced stereotyped behavior, which peaked at 1 hr and disappeared by 4 hr and remained absent for the duration of the infusion. These findings demonstrate that continuous exposure to D1 or D2 agonists caused receptor-selective functional desensitization of D1 or D2 dopamine receptors.(ABSTRACT TRUNCATED AT 250 WORDS)

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗
PubMed1993

Cholinergic lesions of mouse striatum induced by AF64A alter D2 dopaminergic behavior and reduce D2 dopamine receptors and D2 dopamine receptor mRNA.

To determine whether dopamine receptors are expressed in acetylcholine-containing neurons intrinsic to the striatum, and to study further the interactions between the dopaminergic and cholinergic systems, the irreversibly acting cholinergic neurotoxin, ethylcholine mustard aziridinium ion (AF64A), was injected unilaterally into the mouse corpus striatum, and rotational behavior induced by dopamine agonists and certain molecular events associated with this lesion were determined 7 days after lesioning. Brains were analyzed for D2 dopamine receptors by autoradiography, using [3H](-)sulpiride as a ligand, and for D2 dopamine receptor mRNA and glutamic acid decarboxylase mRNA by Northern blot analysis, using selective radiolabelled oligonucleotide probes. Choline uptake sites were determined by binding assays using [3H]hemicholinium-3, a selective choline reuptake blocker, as a ligand. Mice with intrastriatal injections of AF64A showed ipsilateral rotational responses to the non-selective dopamine agonist apomorphine and to the D2 dopamine agonists, pergolide and quinpirole, but not to the D1 dopamine agonist SKF 38393. This was associated with a significant reduction in D2 dopamine receptors in the ipsilateral striatum and a significant decrease in the amount of D2 dopamine receptor mRNA. That AF64A produced a relatively selective cholinergic deficit was supported by the evidence showing that AF64A lesions significantly reduced [3H]hemicholinium-3 binding sites but did not alter glutamic acid decarboxylase (GAD) mRNA. Further, hemicholinium-3, prevented the AF64A-induced changes in rotational behavior. These results suggest that striatal cholinergic interneurons contain D2 dopamine receptors and express the D2 dopamine receptor gene, and that these interneurons are involved in dopamine-mediated rotational behavior.

Animals↗
PubMed1993

Continuously infusing quinpirole decreases Ca2+/calmodulin-dependent phosphorylation in mouse striatum.

Continuously administering the D2 dopamine agonist quinpirole to mice for 6 days produces an initial stereotypy that is reduced by 2 h and is absent from 3 h to the 6 day duration of the infusion. In an attempt to determine the biochemical correlates for this down-regulation of stereotypic behavior, the effects of continuously administering quinpirole on a number of biochemical parameters were measured in mouse corpus striatum. After 6 days of infusion with quinpirole, the striata were analyzed for D1 and D2 dopamine receptors, for the activities of several protein phosphorylation reactions which are thought to be involved in receptor activity and for the levels of calmodulin-binding proteins. Quinpirole decreased the D2 receptors in striatum and produced a small but statistically non-significant increase in D1 receptors, resulting in a significant increase in the ratio of D1 to D2 dopamine receptors. An examination of the effects of quinpirole on protein phosphorylation systems showed that the agonist failed to alter the activity of cyclic AMP-dependent protein kinase or protein kinase C but significantly decreased the Ca2+/calmodulin-dependent phosphorylation of striatal membranes. However, this decrease in Ca2+/calmodulin-dependent phosphorylation was not associated with changes in the levels of calmodulin-binding proteins. The results suggest that behavioral down-regulation following the continuous administration of a D2 dopamine agonist is associated with at least two biochemical events: a down-regulation of D2 dopamine receptors and a decrease of Ca2+/calmodulin-dependent phosphorylation of striatal membranes.

Animals↗
PubMed1993

Continuous treatment with the D2 dopamine receptor agonist quinpirole decreases D2 dopamine receptors, D2 dopamine receptor messenger RNA and proenkephalin messenger RNA, and increases mu opioid receptors in mouse striatum.

Dopamine-mediated behaviors and certain biochemical and molecular events associated with these behaviors were examined following continuous infusion of the D1 dopamine agonist SKF38393 or the D2 dopamine agonist quinpirole into mice for six days. SKF38393 produced a transient grooming behavior while quinpirole initially induced stereotypy, which was followed by an increased locomotor behavior. Continuous infusion of quinpirole caused a significant down-regulation of striatal D2 dopamine receptors without significantly changing the density of D1 receptors. This was accompanied by a decrease in the level of D2 receptor messenger RNA in striatum as measured by Northern analysis. The down-regulation of dopamine receptors was selective for D2 dopamine receptors, since treatment with SKF38393 had no significant effects on either D1 or D2 dopamine receptors, nor did it alter the messenger RNAs for the D1 and D2 receptors. Continuous treatment with quinpirole resulted in a significant increase in striatal mu opioid receptor levels without significant changing delta opioid receptors. This treatment also induced a significant decrease in proenkephalin messenger RNA in striatum. Taken together, these results suggest that the down-regulation of D2 dopamine receptor and D2 receptor messenger RNA is the result of the persistent stimulation of D2 receptors and that the up-regulation of mu opioid receptors may be a compensatory response to a decreased biosynthesis of enkephalin. They suggest further that the biochemical and molecular changes that take place in dopaminergic and enkephalinergic systems following continuous treatment with dopamine agonists may underlie the mechanisms by which certain dopamine-mediated behaviors occur.

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗
PubMed1993

Antisense oligodeoxynucleotide inhibits D2 dopamine receptor-mediated behavior and D2 messenger RNA.

There are several subtypes of dopamine receptors in the central nervous system which mediate the actions of dopamine in producing its diverse motor and behavioral effects. In this study we determined whether an antisense oligodeoxynucleotide directed to the mRNA encoding one of the subtypes of the dopamine receptor can inhibit a specific dopamine-mediated behavior. Accordingly, the effects of a phosphorothioate-modified antisense oligodeoxynucleotide targeted toward the D2 dopamine receptor mRNA (D2 antisense) was studied in mice with unilateral 6-hydroxydopamine-induced lesions of the corpus striatum. Rotational behavior in response to different agents, and the levels of D2 and D1 dopamine receptors and D2 and D1 dopamine receptor mRNAs in corpus striatum were then measured. In control mice, lesioning resulted in a contralateral rotational behavior in response to the D1 dopamine receptor agonist SKF 38393, the D2 dopamine agonist quinpirole, and the muscarinic cholinergic agonist oxotremorine. Lesioning also caused an increase in D2 dopamine receptor mRNA levels in the dorsolateral striatum. Intraventricular injections of the D2 antisense inhibited rotational behavior induced by quinpirole but not that induced by SKF 38393 or that induced by oxotremorine. Repeated administration of the D2 antisense significantly reduced the levels of the D2 dopamine receptor and D2 dopamine receptor mRNA in the dorsolateral but not the dorsomedial striatum. Similar treatment failed to significantly alter the levels of the D1 dopamine receptor or D1 receptor mRNA in dorsolateral or dorsomedial striatum.(ABSTRACT TRUNCATED AT 250 WORDS)

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗
PubMed1993

Localization of the multiple calmodulin messenger RNAs in differentiated PC12 cells.

Calmodulin, a ubiquitous calcium-binding protein which is involved in many biological processes, including cell proliferation and differentiation, has been shown to be encoded by three genes from which five calmodulin messenger RNAs are transcribed. In our previous studies, using the PC12 pheochromocytoma cell line as a model system for neuronal differentiation, all five calmodulin messenger RNAs were found to be present, and treatment with both nerve growth factor and dibutyryl cyclic AMP, which induce neurite outgrowth in these cells, increased the level of calmodulin and differentially increased the levels of the various calmodulin messenger RNAs. In an attempt to uncover the nature of the differential increase in the calmodulin messenger RNAs during neuronal differentiation, we examined here the subcellular distribution of the individual calmodulin messenger RNAs in PC12 cells treated with nerve growth factor and dibutyryl cyclic AMP by in situ hybridization cytochemistry, using radiolabeled oligodeoxynucleotide probes. Using an oligodeoxynucleotide probe which detects all of the calmodulin transcripts, the calmodulin messenger RNAs were found to be distributed throughout the cell bodies of differentiated PC12 cells; significant amounts of calmodulin messenger RNAs were also found in most neurites (approximately 70% of the total number). Using specific probes for the calmodulin messenger RNAs derived from each calmodulin gene, distinct patterns of localization of the different calmodulin messenger RNAs were revealed. The messenger RNAs from calmodulin genes I and II were readily detected in all cell bodies and in about one-half of the neurites. In contrast, a weak signal for the messenger RNAs from calmodulin gene III was associated with cell bodies, while no significant signal was found in neurites. A population distribution analysis of the labeling of individual PC12 cell bodies, as determined by counting autoradiographic grains, revealed differences in the relative abundance of each group of messenger RNAs derived from each of the three calmodulin genes. The order of relative abundance of the messenger RNAs in cell bodies was found to be: calmodulin gene II messenger RNA > calmodulin gene I messenger RNAs >> calmodulin gene III messenger RNAs. An analysis of the labeling density along neurites indicated a similar density of neuritic messenger RNAs from calmodulin gene I and calmodulin gene II, whereas there was no significant signal for the messenger RNAs from calmodulin gene III.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1993

Cognitions, depressive symptoms, and development in adolescents.

This study examined the generalizability of cognitive models of depression to adolescents and explored developmental differences with regard to depressotypic cognitions. Self-reported depressive symptoms and various hypothesized cognitive correlates (e.g., automatic thoughts, attributions, dysfunctional attitudes) were investigated in a sample of 688 adolescents in grades 7 through 12. Measures of normative adolescent cognitions (e.g., egocentrism, self-consciousness) also were included. There was a strong association between negative thinking and depression in adolescents. There was no association between depressogenic thinking and age, nor did the strength of the association between negative cognitions and depression vary from early to middle adolescence. Finally, negative cognitions were associated with self-report measures of both depressive and anxious symptoms.

Adolescent↗
PubMed1993

Behavioral and emotional problems among Thai and American adolescents: parent reports for ages 12-16.

We studied adolescents' behavioral and emotional problems in the United States and in Thailand, a Buddhist country in which, reportedly, aggression is discouraged and self-control, emotional restraint, and social inhibition are encouraged. Standardized parent reports on 118 problems revealed 45 Thai-U.S. differences. Thai adolescents were reported to show more overcontrolled problems (e.g., shyness, compulsivity, inhibition of talking, fearfulness, and constipation) than American adolescents (p < .0001). The two groups did not differ reliably in total undercontrolled problems, but Americans showed higher levels of direct, overt, and interpersonally aggressive undercontrol (e.g., fighting and bullying), whereas Thais showed more indirect and subtle undercontrol that was not interpersonally aggressive (e.g., sulking and sullenness). The findings suggest that different cultures may be linked to different styles of adolescent problem behavior.

Adolescent↗
PubMed1993

A human pseudoautosomal gene, ADP/ATP translocase, escapes X-inactivation whereas a homologue on Xq is subject to X-inactivation.

We report the cloning of a highly conserved pseudoautosomal gene on the human sex chromosomes. A cDNA clone was selected by crosshybridization with a microdissected clone from the chromosomal subregion Xp22.3. It encodes a previously characterized member of the ADP/ATP translocase family and plays a fundamental role in cellular energy metabolism. This gene, ANT3, is located approximately 1,300 kilobases from the telomere, proximal to the pseudoautosomal gene CSF2RA, and escapes X-inactivation. Interestingly, a homologue of ANT3, ANT2, maps to Xq and is subject to X-inactivation. These genes provide the first evidence of two closely related X-chromosomal genes, which show striking differences in their X-inactivation behaviour.

Animals↗
PubMed1993

Parent reports of behavioral and emotional problems among children in Kenya, Thailand, and the United States.

The behavioral and emotional problems children develop may differ from one cultural context to another. We explored this possibility, comparing 11-15-year-old Embu children in Kenya, Thai children, African-American children, and Caucasian-American children. Standardized parent reports on 118 problems revealed 62 significant (p < .01) culture effects. Caucasian-Americans were rated particularly high on undercontrolled problems (e.g., arguing, disobedient at home, cruel to others). Embu children were rated particularly high on overcontrolled problems (e.g., fears, feels guilty, somatic concerns), largely because of the numerous somatic problems reported. The findings may relate to the strict emphasis on compliance and obedience among the Embu, as opposed to the greater independence permitted in the United States. But alternative interpretations are discussed as well, including the effects of parent sensitivities and Third World living conditions.

Adolescent↗
PubMed1993

AF64A lesions of mouse striatum result in ipsilateral rotations to D2 dopamine agonists but contralateral rotations to muscarinic cholinergic agonists.

Behavioral and anatomical evidence supports an interaction between the dopaminergic and cholinergic systems in regulating certain behavioral conditions and motor functions. In this study, we utilized the cholinotoxin, acetylethylcholine mustard aziridinium ion (AF64A), to lesion the mouse corpus striatum in order to examine the role of cholinergic interneurons in striatum on cholinergic- and dopaminergic-mediated rotational behavior. Mice were unilaterally lesioned with AF64A and then challenged with a variety of dopaminergic and cholinergic agonists and antagonists. The results show that mice with AF64A-induced lesions rotate ipsilaterally to challenge doses of the dopamine agonists, apomorphine and pergolide, but rotate contralaterally to challenge injections of the cholinergic agonist, oxotremorine. The gamma aminobutyric acid (GABA) agonist, muscimol, and the M1 agonist, (4-hydroxy-2-butynyl)-1-trimethylammonium m-chlorocarbanilate chloride failed to elicit rotational behavior. The D1 dopamine receptor antagonist, R(+)-7-chloro-8-hydroxy-3-methyl-1-phenyl- 2,3,4,5-tetrahydro-1H-3-benzazepine hydrochloride, inhibited rotations induced by apomorphine at concentrations 10-fold lower than those needed to block the effects of pergolide. However, the D2 dopamine receptor antagonist, sulpiride, blocked pergolide-induced rotations at concentrations about 4-fold lower than those needed to inhibit apomorphine-induced rotational behavior. Atropine blocked oxotremorine-induced contralateral rotations but enhanced apomorphine- and pergolide-induced ipsilateral rotations induced in AF64A-lesioned mice. Atropine was 10 times more effective in blocking oxotremorine-induced rotations than was the M3 antagonist, 4-diphenylacetoxy-N-methyl piperidine methiodide, and was 100 times more potent than the M2 and M1 antagonist, N,N'-bis[6-[[(2- methoxyphenyl)methyl]amino]hexyl]-1,8-octanediamine tetrahydrochloride, or the M1 antagonist, pirenzepine.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1992

Triazolam blocks the initial rotational effects of quinpirole but permits the later developing reduction of dopamine D2-mediated rotational behavior and dopamine D2 receptors.

Continuous infusion of the dopamine D2 receptor agonist quinpirole into mice with unilateral striatal 6-hydroxydopamine lesions initially produces a supersensitive rotational behavior. This is followed by reductions of dopamine D2-mediated behavior and dopamine D2 receptors. In this study we attempted to determine if it is possible to inhibit the acute increase in D2-mediated behavior while still allowing the reduction of D2-mediated behavioral responses and dopamine D2 receptors to occur. Mice were implanted with Alzet minipumps containing either quinpirole alone or quinpirole combined with the GABA receptor modulator triazolam or the dopamine D2 receptor antagonist sulpiride, and rotational behavior was monitored for the 6 days of infusion. The pumps were then removed, and D2 receptors in striatal membranes were determined. Triazolam completely blocked the initial rotational behavior normally induced by implanting quinpirole. However, the quinpirole-induced reduction of D2-mediated behavioral responses and D2 receptors still occurred. Continuous infusion of sulpiride also inhibited the rotational behavior produced by quinpirole, but it prevented the reduction of dopamine D2 receptors. We conclude that up-regulated dopamine receptors and dopaminergic behaviors can be reversed by the continuous administration of a dopamine receptor agonist and that this reversal can occur without producing an initial exacerbation of dopaminergic responses. These results suggest that this type of treatment regimen might be useful for treating clinical conditions associated with dopaminergic supersensitivity.

Analysis of Variance↗