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  • 1
    Electronic Resource
    Electronic Resource
    Classical and non-classical neuroleptics induce supersensitivity of nigral GABA-ergic mechanisms in the rat (1982)
    Springer
    Psychopharmacology 78 (1982), S. 180-184 
    Details
    ISSN: 1432-2072
    Keywords: Neuroleptics ; Substantia nigra ; GABA ; Supersensitivity ; Rotation-rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The present study compared the ability of neuroleptic and non-neuroleptic agents to modify the sensitivity of nigral, GABA-sensitive, non-dopaminergic efferents in the rat after sub-chronic administration. Pre-treatment with haloperidol or clebopride, 1.0 mg/kg PO for 10 days, induced dupersensitivity to the behavioural effects of unilateral intranigral muscimol, 5.0 ng, on withdrawal day 1. This effect was no longer significant in other rats tested on withdrawal day 7. In contrast, similar pre-treatment with sulpiride, 20 mg/kg PO, led to significantly enhanced responses to intra-nigral muscimol on both withdrawal days. Pre-treatment with clozapine, 20 mg/kg, or thioridazine, 12 mg/kg PO, did not lead to supersensitivity on withdrawal day 1, but did so on withdrawal day 7. Pre-treatment with amitriptyline, 20 mg/kg PO, or metoclopramide, 1.0 mg/kg PO, failed to result in supersensitivity on either withdraway day. The data confirm previous biochemical and behavioural findings suggesting that repeated administration of neuroleptics can induce nigral GABA-ergic supersensitivity in the rat, but demonstrate that this action is not an exclusive property of classical, cataleptogenic agents.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00432259
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  • 2
    Electronic Resource
    Electronic Resource
    Biochemical and behavioural properties of clozapine (1989)
    Springer
    Psychopharmacology 99 (1989), S. S6 
    Details
    ISSN: 1432-2072
    Keywords: Clozapine ; D-1 Blockade ; Behavioural effects
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The selection and early development of clozapine was based upon its gross behavioural, arousal-inhibiting, sleep-promoting, and caudate spindle-prolonging properties. Compared to classical neuroleptics, clozapine causes only a short-lasting elevation of plasma prolactin levels, elevates both striatal homovanillic acid and dopamine content, is devoid of marked apomorphine-inhibitory or cataleptogenic activity and fails to induce supersensitivity of striatal dopaminergic systems after chronic administration. Clozapine's intrinsic anticholinergic activity, while stronger than that of other neuroleptic agents, does not appear to underlie either its failure to induce tardive dyskinesias or its superior antipsychotic activity. Furthermore, the overlap between clozapine and several classical neuroleptics with regard to alpha-adrenergic-, serotonin- and histamine-blocking activity makes it unlikely that one or more of these properties is the key to its atypical characteristics. More recent findings show that clozapine and classical neuroleptics differ with regard to their indirect effects on nigral GABA-ergic mechanisms implicated in the induction of tardive dyskinesias and, possibly in keeping with this, that clozapine and similar agents exhibit preferential blockade of D-1 dopamine receptors in the whole animal. Such an action of clozapine in man could well explain both its low EPS liability and, in some subjects, its superior antipsychotic activity.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00442552
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  • 3
    Electronic Resource
    Electronic Resource
    Potentiation of LON 954 tremor by typical and atypical neuroleptics — an indication of striatal dopamine antagonism (1980)
    Springer
    Psychopharmacology 67 (1980), S. 177-180 
    Details
    ISSN: 1432-2072
    Keywords: Tremor ; LON 954 ; Neuroleptics ; Dopamine ; Cyclic AMP
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Tremor produced in laboratory mice by the benzylimidoylurea derivative LON 954 was potentiated in a dose-dependent manner by a variety of typical and atypical neuroleptics. The most effective agents in this respect were those shown by other workers to have a selective action at dopamine receptors, notably the butyrophenones, thioxanthines and fluphenazine. Chlorpromazine and prochlorperazine produced inconsistent effects while clozapine and loxapine respectively delayed and prolonged the peak tremor response. While these findings support primary involvement of striatal dopaminergic mechanisms in LON 954 tremorogenesis, a reduction in cyclic AMP levels may be an important factor in the observed effects.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00431974
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  • 4
    Electronic Resource
    Electronic Resource
    Modification of nigral kainic acid-induced ipsilateral circling behaviour in the rat by neuroleptics and by contralateral caudate ablation (1984)
    Springer
    Psychopharmacology 84 (1984), S. 526-530 
    Details
    ISSN: 1432-2072
    Keywords: Substantia nigra ; Rotational behaviour ; Kainic acid ; Neuroleptics ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract A study was performed to examine possible changes in excitatory amino acid sensitivity within the pars reticulata of the rat substantia nigra as a result of neuroleptic exposure. Unilateral application of 20 ng kainic acid into caudal regions of the pars reticulata resulted in ipsilateral circling behaviour. This activity was significantly reduced 7 days after administration of the depot neuroleptic fluphenazine decanoate, 10.0 mg/kg SC, or 1 h after pretreatment with haloperidol, 0.1–1.0 mg/kg IP. The inhibitory effect of 0.1 mg/kg haloperidol was unaffected by prior ablation of the ipsilateral striatum, which by itself had no effect on the kainate-induced response. However, contralateral caudate ablation 21 days prior to intra-nigral kainate resulted in a markedly enhanced response, although 0.1 mg/kg haloperidol appeared to retain its inhibitory action when tested in such animals. The experimental data suggest a compensatory role of contralateral striatal mechanisms in nigral kainate-induced ipsilateral circling behaviour in the rat. Furthermore, they demonstrate at least a modulatory role of central dopaminergic mechanisms in such elicited behaviour. This latter action may involve multiple basal ganglia sites or, more probably, occur in other brain areas such as the mesolimbic system.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00431460
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  • 5
    Electronic Resource
    Electronic Resource
    Apomorphine response plasticity in lesioned rats: Supersensitivity dependency and lack of drug- or non-drug-associated environmental cuing (1986)
    Springer
    Psychopharmacology 90 (1986), S. 253-258 
    Details
    ISSN: 1432-2072
    Keywords: Apomorphine ; Circling behaviour ; Drug cuing ; Lesions ; Reverse tolerance ; Supersensitivity ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Low doses of apomorphine can induce biphasic, contralateral circling behaviour in rats having unilateral, 6-hydroxydopamine lesions of the substantia nigra. The present studies examined the extent to which this is linked to the supersensitive state, the possible contribution of apomorphine's actions in the intact striatum, and the extent to which response differentiation might be linked to drug-or non-drug-associated environmental cuing. In the first instance, weekly administration of 0.4 mg/kg SC apomorphine to “normosensitive” rats having electrolytic ablation of one caudate failed to result in biphasic circling, whereas clear biphasic responses developed in supersensitive, 6-hydroxydopamine lesioned animals receiving 0.05 mg/kg SC apomorphine at weekly intervals. In the second instance, 6-hydroxydopamine-lesioned animals exhibiting biphasic responses after three exposures to apomorphine continued to do so after additional electrolytic ablation of the contralateral caudate, indicating a primary role for apomorphine's interaction within the denervated striatum. In studying the possible role of drug- or non-drug-associated environmental cuing effects it was found that repeated exposure of 6-hydroxydopamine-lesioned rats to 0.05 mg/kg SC apomorphine at 2-h intervals failed to elicit biphasic responses, although these were evident when the same animals were tested 1 and 2 weeks later. However, studies combining weekly exposure to the test cages with saline or apomorphine administration failed to reveal a role of drug- or non-drug-associated environmental cuing in response differentiation. The latter findings are supported by those from supplementary studies employing opaque contact lenses, in which lesioned animals continued to respond biphasically to apomorphine when deprived of visual input. Taken together, the findings show biphasic responsiveness to apomorphine to be entirely a reflection of the drug's interaction with supersensitive dopamine systems.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00181252
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  • 6
    Electronic Resource
    Electronic Resource
    Nigral actions of GABA agonists are enhanced by chronic fluphenazine and differentiated by concomitant flurazepam (1982)
    Springer
    Psychopharmacology 76 (1982), S. 294-298 
    Details
    ISSN: 1432-2072
    Keywords: Substantia nigra ; GABA agonists ; Super-sensitivity ; Circling
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Unilateral intranigral administration of baclofen (50–200 ng), muscimol (2.5–20 ng), or THIP (50–400 ng) in the rat led to contralateral circling behavior of a qualitatively similar nature. The potency of all three GABA-mimetics was enhanced in animals which had received the depot neuroleptic fluphenazine decanoate (10 mg/kg SC) 7 days prior to their intranigral administration. Significant differences between the nigral actions of the drugs could be demonstrated by their altered activity in the presence of a benzodiazepine. Flurazepam (500 ng) enhanced the intranigral potency of THIP, but reduced that of intranigral baclofen. Muscimol-induced circling behavior was unaffected by concomitant flurazepam. The data provide evidence for a functional supersensitivity of GABA-sensitive nondopaminergic projections from the substantia nigra in response to chronic neuroleptic treatment and reveal differences between the precise sites or modes of action of baclofen, muscimol, and THIP within this structure.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00432565
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  • 7
    Electronic Resource
    Electronic Resource
    The production of an alternative laboratory model of the Parkinson syndrome using a new benzylimidoylurea derivative LON 954 (1977)
    Springer
    Psychopharmacology 52 (1977), S. 165-171 
    Details
    ISSN: 1432-2072
    Keywords: Tremor ; Antiparkinson drugs ; Dopaminergic systems
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract N-carbamoyl-2-(2,6-dichlorophenyl) acetamidine hydrochloride (LON 954) causes a reproducible rest tremor in mice, of rapid onset and short duration with no associated rigidity or akinesia and in the absence of any marked changes in body temperature or accompanying peripheral parasympathomimetic effects. This tremor can be antagonised by the dopamine receptor agonists l-Dopa, bromocriptine, nomifensine and piribedil, as well as by anticholinergic anti-Parkinson drugs having an inhibitory effect on dopamine uptake such as benapryzine and benztropine. In contrast, benzhexol, orphenadrine and amantadine had no effect. LON 954 appears to be more specific than oxotremorine for the detection of drugs having therapeutic potential in the treatment of Parkinson's disease, particularly those exerting their effect through dopaminergic systems. An antagonist (BS 100–141), which is a structural isomer of LON 954, is also described.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00439104
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