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  • 1
    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
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  • 2
    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
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