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  • Electronic Resource  (11)
  • Cell & Developmental Biology  (4)
  • MK-801  (4)
  • Rat  (3)
  • 1
    ISSN: 1435-1463
    Keywords: Keywords: Serotonin ; glutamate ; schizophrenia ; MK-801 ; d-amphetamine ; M100907.
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary. The purpose of the present study was to compare the effectiveness of the selective 5-HT2A antagonist M100907 in different psychosis models. The classical neuroleptic haloperidol was used as reference compound. Two hyperdopaminergia and two hypoglutamatergia mouse models were used. Hyperdopaminergia was produced by the DA releaser d-amphetamine or the DA uptake inhibitor GBR 12909. Hypoglutamatergia was produced by the un-competitive NMDA receptor antagonist MK-801 or the competitive NMDA receptor antagonist D-CPPene. M100907 was found to counteract the locomotor stimulant effects of the NMDA receptor antagonists MK-801 and D-CPPene, but spontaneous locomotion, d-amphetamine- and GBR-12909-induced hyperactivity were not significantly affected. Haloperidol, on the other hand, antagonized both NMDA antagonist- and DA agonist-induced hyperactivity, as well as spontaneous locomotion in the highest dose used. Based on the present and previous results we draw the conclusion that 5-HT2A receptor antagonists are particularly effective against behavioural anomalies resulting from hypoglutamatergia of various origins. The clinical implications of our results and conclusions would be that a 5-HT2A receptor antagonist, due to i a the low side effect liability, could be the preferable treatment strategy in various disorders associated with hypoglutamatergia; such conditions might include schizophrenia, childhood autism and dementia disorders.
    Type of Medium: Electronic Resource
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  • 2
    Electronic Resource
    Electronic Resource
    Springer
    Experimental brain research 56 (1984), S. 144-148 
    ISSN: 1432-1106
    Keywords: Rat ; Parabigeminal nucleus ; Superior colliculus ; Lateral geniculate nucleus ; HRP
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The retino-recipient layers of the superior colliculus project predominantly to the dorsal and ventral divisions of the ipsilateral parabigeminal nucleus, while receiving an input chiefly from the medial division of the contralateral nucleus. A variety of retrograde tracing techniques was used to confirm that there is a projection from the medial division of the parabigeminal nucleus to the contralateral dorsal lateral geniculate nucleus in normal adult hooded rats. Some parabigeminal cells branch to supply both dorsal lateral geniculate nucleus and retino-recipient layers of the superior colliculus.
    Type of Medium: Electronic Resource
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  • 3
    Electronic Resource
    Electronic Resource
    Springer
    Psychopharmacology 113 (1993), S. 177-186 
    ISSN: 1432-2072
    Keywords: Rat ; Behavior ; Microstructure ; Scaling measures
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Previous studies demonstrated that drug effects on the movement sequences of rats in unconditioned motor activity paradigms can be quantified by scaling measures that describe the average relationship between a variable of interest and an experimental parameter. However, rats engage in a wide variety of geometrically distinct movements that can be influenced differentially by drugs. In this investigation, the extended scaling approach is presented to capture quantitatively the relative contributions of geometrically distinct movement sequences to the overall path structure. The calculation of the spectrum of local spatial scaling exponents,f(d), is based on ensemble methods used in statistical physics. Results of thef(d) analysis confirm that the amount of motor activity is not correlated with the geometrical structure of movement sequences. Changes in the average spatial scaling exponent,d, correspond to shifting the entiref(d) function, and indicate overall changes in path structure. With the extended scaling approach, straight movement sequences are assessed independently from highly circumscribed movements. Thus, thef(d) function identifies drug effects on particular ranges of movement sequences as defined by the geometrical structure of movements. More generally, thef(d) function quantifies the relationship between microscopically recorded variables, in this paradigm consecutive (x, y) locations, and the macroscopic behavioral patterns that constitute the animal's response topography.
    Type of Medium: Electronic Resource
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  • 4
    ISSN: 1432-2072
    Keywords: Rat ; Behavior ; Microstructure ; Dopamine releasers ; Dopamine uptake inhibitors
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The effects of four indirect dopamine agonists,d-amphetamine (0.25–4.0 mg/kg), cocaine (2.5–40.0 mg/kg), GBR 12909 (10.0–30.0 mg/kg), and nomifensine (5.0–20.0 mg/kg), on the behavioral organization of movements in an unconditioned motor paradigm were investigated in rats. The extended scaling hypothesis using the fluctuation spectrum of local spatial scaling exponents was used to quantify the geometrical characteristics of movements. The results reveal a qualitatively similar disruption of behavioral organization by lower doses of these drugs. Specifically, rats treated withd-amphetamine (〈2.0 mg/kg), cocaine (〈20.0 mg/kg), GBR 12909 (〈20.0 mg/kg), or nomifensine (〈10.0 mg/kg) exhibited a reduced range in the fluctuation spectrum, reflecting a predominance of meandering movements with local spatial scaling exponents between 1.3 and 1.7. This reduction was accompanied dynamically by a reduced predictability of movement sequences as measured by the dynamical entropy,h. By contrast, higher doses of these drugs produced distinctly different changes in behavioral organization. In particular, 4.0 mg/kgd-amphetamine and 40.0 mg/kg cocaine increased the fluctuation range, reflecting relative increases in both straight and circumscribed movements that are interpreted as a combination of spatially extended and local perseveration. In contrast, high doses of 30.0 mg/kg GBR 12909 and 20.0 mg/kg nomifensine induced only local perseveration. High doses ofd-amphetamine, cocaine, GBR 12909 and nomifensine reduced the dynamical entropy,h, indicating an increased predictability of the movement sequences. These results suggest that the generic behavioral change induced by low doses of dopamine agonists is characterized by a reduced variety of path patterns coupled with an increased variability in sequential movement sequences. The differential effects of higher doses of these drugs may be due to their influences on other neurotransmitter systems or differential affinities for different dopamine subsystems.
    Type of Medium: Electronic Resource
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  • 5
    ISSN: 1435-1463
    Keywords: Keywords: MDL100907 ; M100907 ; MK-801 ; locomotion ; schizophrenia ; serotonin ; mouse ; psychosis ; monoaminergic biochemistry.
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary. The locomotor stimulation induced by the N-methyl-D-aspartate (NMDA) receptor antagonist MK-801 (dizocilpine) in mice was regarded as a model of at least some aspects of schizophrenia. The serotonin synthesis inhibitor dl-p-chlorophenylalanine (PCPA) was used to evaluate the involvement of endogenous serotonin in (a) the induction of MK-801-induced hyperlocomotion in NMRI mice, and (b) the inhibition of MK-801-induced hyperlocomotion by each of five monoaminergic antagonists (M100907, clozapine, olanzapine, raclopride, SCH23390). Further, brain monoaminergic biochemistry was characterised in rats and mice after various drug treatments. PCPA pretreatment did not significantly reduce MK-801-induced hyperlocomotion in any of the experiments performed; however in a meta-analysis of six experiments, the locomotion displayed by MK-801-treated animals was diminished 17% by PCPA pretreatment. The selective 5-HT2A receptor antagonist M100907 exerted a dose-dependent inhibition of MK-801-induced hyperlocomotion. This effect was abolished in mice pretreated with PCPA, but could be restored in a dose-dependent manner by restitution of endogenous 5-HT by means of 5-hydroxytryptophan (5-HTP). On the other hand, the inhibition of MK-801-induced hyperlocomotion exerted by the selective dopamine D-2 receptor antagonist raclopride or the dopamine D-1 receptor antagonist SCH23390 was unaffected by PCPA pretreatment. The antipsychotics clozapine and olanzapine displayed a split profile. Hence, the inhibitory effect on MK-801-induced hyperlocomotion exerted by low doses of these compounds was diminished after PCPA pretreatment, while inhibition exerted by higher doses was unaffected by PCPA. These results suggest that (1) MK-801-induced hyperlocomotion is accompanied by an activation of, but is not fully dependent upon, brain serotonergic systems. (2) In the hypoglutamatergic state induced by MK-801, endogenous serotonin exerts a stimulatory effect on locomotion through an action at 5-HT2A receptors, an effect that is almost completely counterbalanced by a concomitant inhibitory impact on locomotion, mediated through stimulation of serotonin receptors other than 5-HT2A receptors. M100907, by blocking 5-HT2A receptors, unveils the inhibitory effect exerted on locomotion by these other serotonin receptors. (3) Dopamine D-2 receptor antagonistic properties of antipsychotic compounds, when they come into play, override 5-HT2A receptor antagonism. Possible implications for the treatment of schizophrenia with 5-HT2A receptor antagonists are discussed. It is hypothesized that treatment response to such agents is dependent on increased serotonergic tone.
    Type of Medium: Electronic Resource
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  • 6
    ISSN: 1435-1463
    Keywords: MK-801 ; locomotion ; ritanserin ; M100907
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The apparent antipsychotic action of the selective 5-HT2a receptor antagonist M100907 in MK-801-treated NMRI mice was shown to be markedly counteracted by the 5-HT2a/2c receptor antagonist ritanserin. The mechanism of action and potential implications are discussed.
    Type of Medium: Electronic Resource
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  • 7
    Electronic Resource
    Electronic Resource
    Springer
    Journal of neural transmission 95 (1994), S. 113-121 
    ISSN: 1435-1463
    Keywords: NMDA receptors ; DA receptors ; MK-801 ; SCH 23390 ; raclopride ; locomotor activity ; schizophrenia
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The present study was aimed at clarifying to what extent the hypermotility induced by the uncompetitive N-methyl-D-aspartate (NMDA) antagonist MK-801 depends on dopamine (DA) D-1 compared to D-2 receptor tone. The D-1 receptor antagonist SCH 23390 was found to reduce locomotion to a greater extent in MK-801-treated than in vehicle-treated mice, whereas the reverse appeared to be the case for the DA D-2 receptor antagonist raclopride. In other words, MK-801-induced hyperactivity was more readily antagonized by SCH 23390 than by raclopride and, thus, DA D-1 receptors seem to be more important than D-2 receptors for MK-801-induced hyperactivity. These results are in line with our previous observation that MK-801 generally interacts synergistically with a DA D-1 but not with a D-2 receptor agonist in monoamine-depleted mice. In view of the possible role of deficient glutamatergic neurotransmission in schizophrenia, our findings underline the importance of investigating the efficacy of selective DA D-1 antagonists in this disorder.
    Type of Medium: Electronic Resource
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  • 8
    Electronic Resource
    Electronic Resource
    New York, N.Y. : Wiley-Blackwell
    Journal of Cellular Biochemistry 48 (1992), S. 141-149 
    ISSN: 0730-2312
    Keywords: laminin ; structure-function ; adhesion ; Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Chemistry and Pharmacology , Medicine
    Notes: Mouse PFHR9 laminin, B1B2-heterodimers, and free B1-chains were separated from one another by gel filtration on superose 6. The cell attachment promoting activity of these species was measured after immunoprecipitation with monoclonal anti-laminin antibodies coupled to Sepharose 6MB beads. These antibodies, Which did not react with the laminin E8 fragment, were directed against epitopes in the NH2-terminus of the laminin B1-chain and in the central region of laminin. After incubation with purified EHS laminin, the immunosorbents revealed efficient adhesion substrates for a rat rhabdomyosarcoma cell line which attached preferentially to the laminin E8 fragment. Although both were immunoprecipitated efficiently, B1B2-heterodimers and B1-chains, unlike PFHR9 laminin, did not support the attachment of RMS cells. On a molar basis B1B2-heterodimers were 24 times less efficient than PFHR9 laminin or EHS laminin in supporting cell attachment. These data suggest that heterotrimeric configuration is essential to the adhesive function of the laminin E8 fragment.
    Additional Material: 5 Ill.
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  • 9
    ISSN: 1058-8388
    Keywords: Muscle differentiation ; Fetal mouse hindlimb ; Gene expression ; Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine
    Notes: The modulation of contractile protein gene expression in mouse crural muscles (i.e., muscles located in the region between the knee and ankle) during the fetal period (defined as 15 days gestation to birth), resulting in diversity among and within these muscles, has been evaluated with in situ hybridization and correlated with morphogenetic events in the extensor digitorum longus and soleus muscles. During the fetal period extensive secondary myotube formation occurs in the crural muscles, and the myotubes become innervated (Ontell and Kozeka [1984a, b] Am. J. Anat. 171:133-148, 149-161; Ontell et al. [1988a, b] Am. J. Anat. 181:267-278, 181:278-288). At 15 days gestation, hybridization with 35S-labeled antisense cRNA probes demonstrates the accumulation of transcripts forα-cardiac andα-skeletal actin; MLC1A, MLC1F, and MLC3F; and MHCemb, MHCpn, and MHCβ/slow. At 16 days gestation, accumulation of MHCemb transcripts is reduced (as compared with earlier developmental stages); intensity of signal following hybridization with the probe forα-skeletal actin is, for the first time, equal to that for the cardiac isoform; and MLC1V mRNA accumulation is discernible. At this stage, variation in transcript accumulation for some mRNAs among and within crural muscles becomes evident. Two factors may play a role in the selective distribution of these transcripts: (1) the stage of muscle maturation; and (2) the future myofiber type. At 16 days gestation anterior crural muscles (which mature ˜ 2 days before posterior crural muscles; Ontell and Kozeka [1984a, b], ibid., Ontell et al. [1988a, b], ibid.) exhibit a greater accumulation of transcripts forα-skeletal actin and for MLC3F than is found in posterior crural muscles. In muscles that in the neonate are composed, in large part, of slow myofibers, MHCβ/slow and MLC1V mRNAs accumulate in greater amounts, whereas MHCpn transcripts are less abundant in the soleus muscle than in other crural muscles. By 19 days gestation regionalization of transcript accumulation is more pronounced. The soleus muscle, a predominantly slow twitch muscle in the newborn mouse (Wirtz et al. [1983] J. Anat. 137:109-126) exhibits strong signal after hybridization with probes specific for MHCβ/slow and MLC1V. While the level of transcript accumulation for the developmetal isoforms, MHCemb, MLC1A, andα-cardiac actin, is greatly reduced in most crural muscles at 19 days gestation, these transcripts persist in the soleus muscle at levels equal to or exceeding their amount in limb muscles of 13 day gestation mouse embryos. By 19 days gestation both MyoD and myogenin are “down-regulated” (as compared with their expression at earlier developmental stages) in all muscle masses. Alterations in contractile protein gene expression are correlated with changes in the myogenic regulatory factors present in fetal hindlimbs during development. © 1993 Wiley-Liss, Inc.
    Additional Material: 5 Ill.
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  • 10
    Electronic Resource
    Electronic Resource
    New York, N.Y. : Wiley-Blackwell
    Journal of Cellular Biochemistry 39 (1989), S. 285-292 
    ISSN: 0730-2312
    Keywords: epithelial cells ; putative growth factor ; regression sequence ; androgen-independent epithelial cells ; Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Chemistry and Pharmacology , Medicine
    Notes: A series of rapidly dividing epithelial (RDE) cell lines have been isolated from primary cultures of rat ventral prostate (RVP) epithelial cells. Unlike androgen-dependent secretory epithelial cells, the RDE cells in culture do not express the androgen-dependent secretory proteins, nor do they express the androgen-repressed cell death sequences (TRPM-2) found in the epithelial cells during prostatic regression. Screening of a cDNA clone library established from RDE cell mRNA has yielded a number of RDE cell-specific sequences. One of these, RDE-.25 is a 250-base mRNA. The sequence of RDE-.25 shows considerable homology with the rat growth hormone gene and two murine oncogene sequences. We believe that the absence of androgen-repressed cell death sequence expression confers androgen independence for survival and growth, while the expression of RDE-.25 may represent an autocrine growth stimulus which greatly increases the rate of cell division in these cells.
    Additional Material: 4 Ill.
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