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  • 1
    Electronic Resource
    Electronic Resource
    Antagonism of amphetamine-induced disruption of latent inhibition in rats by haloperidol and ondansetron: Implications for a possible antipsychotic action of ondansetron (1994)
    Springer
    Psychopharmacology 114 (1994), S. 657-664 
    Details
    ISSN: 1432-2072
    Keywords: Latent inhibition ; Dopamine ; Ondansetron ; 5HT3 antagonists ; Amphetamine
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Latent inhibition (LI) is a behavioural phenomenon whereby preexposure to a stimulus without reinforcement interferes with the formation of subsequent associations to that stimulus. Using preexposure to a tone stimulus which subsequently serves as a conditioned stimulus for suppression of licking, we have confirmed that LI is disrupted by a low dose of amphetamine. Haloperidol was able to prevent this effect of amphetamine. Ondansetron, a selective and potent 5HT3 receptor antagonist, was also shown to be effective at blocking the amphetamine-induced disruption of LI at a dose of 0.01 mg/kg, but not at 0.1 mg/kg. In addition, it was demonstrated that ondansetron could enhance LI; using only ten preexposures, no LI was obtained in the saline group, but was apparent in animals given ondansetron, an effect which has been previously shown with haloperidol. Haloperidol, at the higher dose used, reduced suppression of licking, however, ondansetron at the effective dose had no such effect. It is concluded that ondansetron is able to attenuate increases in dopamine activity, produced pharmacologically with amphetamine without affecting baseline dopamine activity. The implications of these findings for a possible antipsychotic action of ondansetron are discussed.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF02244998
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  • 2
    Electronic Resource
    Electronic Resource
    Effects of dopamine and serotonin-releasing agents on methamphetamine discrimination and self-administration in rats (1999)
    Springer
    Psychopharmacology 141 (1999), S. 287-296 
    Details
    ISSN: 1432-2072
    Keywords: Key words Methamphetamine ; Dopamine ; Serotonin ; Phentermine ; Fenfluramine ; Drug-discrimination ; Self-administration ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  To analyze the involvement of dopamine (DA) and serotonin (5-HT) release in the stimulus properties of methamphetamine, two amphetamine analogs that selectively release either brain DA (phentermine) or 5-HT (fenfluramine) were tested for their ability to substitute for methamphetamine in rats discriminating methamphetamine (1.0 mg/kg) from saline. They were subsequently tested for their ability to alter IV methamphetamine (0.06 mg/kg per injection) self-administration in the same species when given as a pretreatment. The DA releaser phentermine, like methamphetamine itself, decreased methamphetamine self-administration (to 70% of baseline responding), but only at a dose of 3.0 mg/kg that fully generalized to the methamphetamine stimulus in the discrimination study. The 5-HT releaser fenfluramine attenuated methamphetamine self-administration to a much larger extent than phentermine (to 37% of baseline responding) at a dose of 1.8 mg/kg that did not generalize to methamphetamine and did not decrease rate of responding in the discrimination study. Tolerance developed to the inhibitory effect of 1.8 mg/kg fenfluramine on methamphetamine self-administration when it was given repeatedly over four consecutive daily sessions. The fenfluramine-induced decrease in methamphetamine self-administration was also attenuated when it was given together with the small 1.0 mg/kg dose of phentermine. These results suggest that DA release plays a dominant role in the discriminative stimulus effects of methamphetamine. However, stimulation of 5-HT release can strongly modify methamphetamine self-administration.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002130050836
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  • 3
    Electronic Resource
    Electronic Resource
    Dopaminergic mechanisms and cognitive deficit in schizophrenia (1979)
    Springer
    Psychopharmacology 63 (1979), S. 273-280 
    Details
    ISSN: 1432-2072
    Keywords: Dopamine ; Lateral inhibition ; Attention ; Schizophrenia ; Model for schizophrenia ; Schizophrenic symptoms
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract A hypothesis is briefly discussed proposing that schizophrenic symptoms are due to a breakdown in a mechanism by which conscious attention is limited and directed. It is shown that this mechanism can be modelled in terms of a simple nerve network in which every channel inhibits all the others. Failure of this inhibition would cause the defect hypothesised to occur in schizophrenia. It is shown that if dopamine is given a central role as transmitter in such a network then the various predictions about the biochemistry of schizophrenia that follow are not only consistent with the evidence for the ‘dopamine theory’ of schizophrenia, but also with much of the evidence held to be contrary to that theory. While not purporting to be an experimentally validated description of schizophrenia, this model goes beyond the single amine theories of schizophrenia and links dysfunctions in amine systems with specific behavioural control mechanisms. Given the current state of knowledge, such models can make only limited predictions about the biochemistry of schizophrenia. However, an attempt to link behavioural and biochemical systems in this way will be crucial for the development of viable animal models of schizophrenia.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00433561
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  • 4
    Electronic Resource
    Electronic Resource
    Nicotine blocks latent inhibition in rats: evidence for a critical role of increased functional activity of dopamine in the mesolimbic system at conditioning rather than pre-exposure (1993)
    Springer
    Psychopharmacology 110 (1993), S. 187-192 
    Details
    ISSN: 1432-2072
    Keywords: Nicotine ; Latent inhibition ; Dopamine ; N. accumbens ; Haloperidol
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Latent inhibition (LI) is a cognitive process whereby repeated exposure of a stimulus without consequence impedes the formation of subsequent associations with that stimulus. A number of studies in the rat have reported that LI is impaired by moderate systemic doses of amphetamine, an effect believed to be mediated via dopamine (DA) release in the nucleus accumbens. We and others have reported that nicotine has a selective effect in releasing DA in the accumbens rather than the caudate nucleus. We have therefore examined the ability of nicotine to disrupt LI, using a conditioned emotional response paradigm. Pre-exposure of a tone stimulus impaired subsequent conditioning between that stimulus and mild footshock, as indexed by suppression of licking by the tone subsequently presented alone. This LI effect was prevented, by an effect confined to the pre-exposed group, by doses of 0.4 or 0.6 mg/kg nicotine SC, which are accumbens selective, given before pre-exposure and before conditioning. The effect of nicotine in disrupting LI was prevented by prior administration of haloperidol at a dose (0.5 mg/kg) reported to reverse the disruptive effect of amphetamine on LI. Although the amphetamine effect requires two administrations, the effect of two administrations of nicotine was reproduced by a single dose of nicotine given before conditioning, but not by a single dose before pre-exposure. The results are discussed in relation to studies in human control and schizophrenic subjects, which suggest that increased DA activity in humans is also associated with impaired LI. The results indicate that nicotine does indeed increase functional DA activity in the rat accumbens; the consequent disruption of LI critically depends upon an action at the time of conditioning, and is independent of processes which occur during pre-exposure. In more general terms, this indicates the potential of drug experiments to complement behavioural studies on the mechanism of latent inhibition.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF02246971
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  • 5
    Electronic Resource
    Electronic Resource
    Behavioural and neurochemical characteristics of phentermine and fenfluramine administered separately and as a mixture in rats (1997)
    Springer
    Psychopharmacology 131 (1997), S. 296-306 
    Details
    ISSN: 1432-2072
    Keywords: Key words Drug discrimination ; Microdialysis ; Dopamine ; Serotonin ; Phentermine ; Fenfluramine
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Clinical case studies suggest that combined administration of the serotonergic agent fenfluramine (FEN) and the weak amphetamine-like anorexic agent phentermine (PHEN) may be useful in the treatment of alcohol and cocaine addictions. The present experiment examined the nature of the interaction between the two agonists using the drug discrimination paradigm. In vivo microdialysis served to examine the neurochemical profile of dopamine and serotonin release in the nucleus accumbens. In conscious rats, acute injections of FEN (1.0–2.0 mg/kg IP) or PHEN (1.0–2.0 mg/kg IP) selectively elevated levels of serotonin and dopamine in the nucleus accumbens, respectively. A mixture (1 mg/kg of each) increased levels of both amines by similar magnitudes to those observed with each individually. Three groups of Sprague-Dawley rats were trained to discriminate (1) FEN (1.0 mg/kg IP) alone, (2) PHEN (1.0 mg/kg IP) alone or a mixture (3) PHEN+FEN (1 mg/kg of each, IP) from saline under a fixed ratio (FR-10) schedule of food reinforcement. Rats acquired the mixture discrimination rapidly, while for the other groups the training dose had to be increased to 2.0 mg/kg to attain stimulus control. The individual components of the mixture at the training dose generalized partially to the mixture, and complete generalisation was observed following 3.0 mg/kg FEN or PHEN. Rats trained to discriminate the individual components showed respective cross-generalisation profiles. Generalisation to cocaine (0.3–10.0 mg/kg IP), amphetamine (0.1–3.0 mg/kg IP) and nicotine (0.1–0.8 mg/kg SC) was greatest in the MIX-trained rats, while partial or no generalisation was observed in rats trained to discriminate the individual compounds. From the present results, it may be concluded that the two drugs given as a mixture do not produce a novel cue. Rather, these aminergics appear to interact additively. Furthermore, the dual stimulation of the amines by the mixture may be the basis for the cueing effects of the FEN+PHEN drug mixture, and its effectiveness in treating drug addictions.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002130050296
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  • 6
    Electronic Resource
    Electronic Resource
    Analysis of the morphology and function of primary cilia in connective tissues:A cellular cybernetic probe? (1985)
    New York, NY : Wiley-Blackwell
    Cell Motility and the Cytoskeleton 5 (1985), S. 175-193 
    Details
    ISSN: 0886-1544
    Keywords: primary cilia ; connective tissues ; secretory organelles ; extracellular matrix ; cybernetic probe ; Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Medicine
    Notes: More than 300 primary cilia have been identified electronmicroscopically in a variety of embryonic and mature connective tissue cells. To further define the enigmatic function of these cilia, we examined the interrelationships between the basal apparatus and cytoplasmic organelles and the ciliary shaft and the extracellular matrix. The basal diplosome was consistently associated with the secretory organelles including the maturing face of the Golgi complex, Golgi vacuoles and vesicles, the microtubular network, the plasma membrane, and coated pits and vesicles. Small vesicles and amorphous granules were also observed within the ciliary lumen and adjacent to the ciliary membrane. Microtubule-membrane bridges linked axonemal tubules to the ciliary membrane. The position, projection, and orientation of the axoneme were influenced by the structural organisation and mechanical properties of the matrix and frequently caused angulation of the ciliary shaft relative to the basal body. Located midway between the secretory apparatus and the extracellular matrix, primary cilia would appear ideally situated to mediate the necessry interaction between the cell and its surrounding environment prerequisite to the formation and maintenance of a functionally effective matrix. We propose that primary cilia in connective tissue cells could act as multifunctional, cellular cybernetic probes, receiving, transducing, and conducting a variety of extrinsic stimuli to the intracellular organelles responsible for effecting the appropriate homeostatic feedback response to changes in the extracellular microenvironment.
    Additional Material: 17 Ill.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/cm.970050302
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  • 7
    Electronic Resource
    Electronic Resource
    The sertoli cell junctional specializations and their relationship to the germinal epithelium as observed after efferent ductule ligation (1975)
    New York, NY [u.a.] : Wiley-Blackwell
    The @Anatomical Record 183 (1975), S. 267-291 
    Details
    ISSN: 0003-276X
    Keywords: Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine
    Notes: Seminiferous tubules from testes of normal and efferent ductule ligated mice were examined with the electron microscope. The tubules in the ligated animals were markedly distended and at most stages of the seminiferous cycle the epithelium exhibited a series of circumferentially-oriented ridges. Cross-sectional profiles of these ridges were studied with particular emphasis on the Sertoli cell junctional specializations and their relationship to the germinal cells.In the ligated specimen the basal cytoplasm of the Sertoli cells is highly attenuated, often appearing as a thin process resting on the basement lamina. Where the cytoplasm of one Sertoli cell ends, it meets in apposition with the cytoplasm of an adjoining Sertoli cell, and at these sites, junctional specializations are present. The ridges are comprised of a stalk of apical Sertoli cell cytoplasm, often appearing like an inverted cone, with young spermatids aligned along the lateral surfaces and the more mature spermatid population embedded within the apical cytoplasm. Junctional specializations were observed along these lateral Sertoli cell surfaces. In some instances, they formed a free surface, but usually early spermatids were in contact with the junctional specializations. With respect to the more mature spermatids, the acrosomal component was typically found in relation to a junctional specialization. Germ cells at the spermatocyte stage were also noted in relation to the Sertoli cell junctional specializations.The findings suggest that spermatocytes cross the Sertoli cell barrier and gain access to the adluminal compartment of the seminiferous tubule through the disengagement of the inter-Sertoli cell junctional complex. It is proposed that when the inter-Sertoli cell junctional specializations separate, the spermatocytes come in apposition with the newly freed junctional surfaces and remain in relation with them through the ensuing divisions. It appears that at some point, firm adhesion between germ cells and the junctional specializations occurs; the spermatid progeny may thus maintain contact with the original inter-Sertoli cell junctional specializations until their release into the tubule lumen.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/ar.1091830205
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  • 8
    Electronic Resource
    Electronic Resource
    The organization of the seminiferous epithelium in the mouse testis following ligation of the efferent ductules. A light microscopic study (1974)
    New York, NY [u.a.] : Wiley-Blackwell
    The @Anatomical Record 180 (1974), S. 565-579 
    Details
    ISSN: 0003-276X
    Keywords: Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine
    Notes: Seminiferous tubules from mouse testes were studied with the light microscope after the efferent ductules had been ligated for 48 hours. As a consequence of ligation, the tubules became markedly distended by the fluid which they accumulated; the epithelium was reduced in height, and exhibited a significantly less complex stratification than in the normal. Longitudinal sections of the distended tubules, particularly those in the early stages of the seminiferous cycle, revealed pillar-like epithelial profiles arranged in a repetitive series. Each “pillar” consisted of Sertoli cell cytoplasm along with two generations of spermatids, the older generation embedded within the Sertoli cell, and the younger generation aligned, one cell above the other, along its sides. Oblique or grazing sections through tubules exhibiting the same stages of spermiogenesis revealed band-like epithelial profiles arranged in parallel array. The two types of epithelial configurations are interpreted as representing a series of circumferentially oriented ridges within the tubule. It is postulated that each spermatid generation within a ridge constitutes a single clone, and that it is the cytoplasmic bridges joining the spermatids, in combination with their attachment to the Sertoli cells, which provide the organization, delineation, and structural stability of the ridges.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/ar.1091800403
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  • 9
    Electronic Resource
    Electronic Resource
    The Sertoli cell junctional specialization during spermiogenesis and at spermiation (1976)
    New York, NY [u.a.] : Wiley-Blackwell
    The @Anatomical Record 186 (1976), S. 79-103 
    Details
    ISSN: 0003-276X
    Keywords: Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine
    Notes: The relationship between developing spermatids and Sertoli cell junctional specializations was studied with the electron microscope during spermiogenesis and at spermiation. At stage I of the seminiferous cycle, the newly formed spermatids are found in apposition to junctional specializations at the lateral surfaces of the Sertoli cell. Visualization of the junctional site of this early stage appears to be dependent on orientation and plane of section. As differentiation proceeds, the spermatids elongate and come to lie within deep recesses of the Sertoli cell. At this time the junctional specialization is limited to the acrosomal portion of the spermatid. During the maturation phase, the spermatids, while maintaining the same relationship to the junctional specialization, approach the lumen. When stage VIII of the cycle is reached, the stage in which spermiation occurs, the spermatids are at the luminal surface. The relationship of the spermatid head to the junctional specializations is quite variable during this stage. Some spermatids are observed still attached to the Sertoli cell at the junctional site, while others are found completely or partially surrounded by Sertoli cytoplasm, but with no evidence of the normally interposed junctional specialization. Yet, in other instances, the spermatids are observed in a position slightly removed from the junctional site. Also evident are profiles of junctional specializations at a free surface of the Sertoli cell, there being no attached spermatid. In some instances the junctional specializations appeared in apposition to a residual body. In the case of the free surface profiles, the junctional specialization at times lined an empty cleft or crypt-like recess, giving the impression that the spermatid head had just been dislodged from the junctional contact site. The findings indicate that the spermatid is in contact with a junctional specialization from its initial appearance and remains so until spermiation is initiated. It is postulated that spermiation is initiated through a physiological change in the junctional specialization resulting in loss of adhesion and consequent release of the sperm head from its attachment site. A similar mechanism is proposed in relation to the inter-Sertoli junctional complex to account for the means by which the spermatocytes cross this barrier to reach the adluminal compartment of the seminiferous epithelium.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/ar.1091860107
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  • 10
    Electronic Resource
    Electronic Resource
    Characterization of Sertoli cell-germ cell junctional specializations in dissociated testicular cells (1979)
    New York, NY [u.a.] : Wiley-Blackwell
    The @Anatomical Record 193 (1979), S. 23-41 
    Details
    ISSN: 0003-276X
    Keywords: Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine
    Notes: To further characterize Sertoli cell-germ cell junctional specializations seminiferous tubules from sexually mature Sprague-Dawley rats were dissociated by enzymatic and mechanical methods. Ultrastructural analysis of cell suspensions prepared by incubation in collagenase alone or by mechanical methods revealed that spermatids remained attached to Sertoli cells or Sertoli cell fragments. Such cellular associations were found only between Sertoli cell fragments and spermatids in which the developing acrosome had made contact with the plasma membrane (step 8 and subsequent steps of spermiogenesis). Furthermore, the fragments were confined to that region of the plasma membrane over the acrosome. The Sertoli cell half of this adhesive site displayed the typical elements of Sertoli cell junctions, filamentous bundles and associated cisterna of endoplasmic reticulum, in apposition to the spermatids. The spermatids demonstrated no surface specializations at the attachment sites. In contrast, in cell suspensions prepared with trypsin, spermatids were free of attachments to Sertoli cells or their fragments. These results demonstrate that: (1) the junctions act to bind cells together, (2) adhesive type contact is established between Sertoli cells and spermatids at step 8 and subsequent steps of spermiogenesis, (3) contact is restricted to the spermatid plasma membrane over the acrosome, and (4) spermatids can be freed from the junctional specializations by treatment with trypsin.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1002/ar.1091930103
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