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  • 1
    ISSN: 1432-2072
    Schlagwort(e): Key words Anxiety ; Benzodiazepine ; β-CCT ; BZ (ω) receptor ; Convulsions ; Diazepam ; In vivo binding ; Mice ; Myorelaxation ; Sedation ; Zolpidem
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract  Rationale: It has been suggested that different BZ (ω) receptor subtypes may mediate distinct behavioural effects of BZ receptor ligands. Objective: The present study examined this hypothesis further. Methods: The antagonism exerted by the selective BZ1 (ω1) receptor antagonist β-CCT on the pharmacological effects of the selective BZ1 (ω1) receptor agonist zolpidem and the non-selective BZ (ω) receptor agonist diazepam in behavioural, biochemical and electrophysiological experiments was assessed. Results:β-CCT which was devoid of activity per se, antagonized the effects of the non-selective BZ (ω) receptor full agonist diazepam and the selective BZ1 (ω1) receptor full agonist zolpidem against seizures produced by isoniazid, but β-CCT failed to affect their action on seizures produced by pentylenetetrazole (PTZ), suggesting that BZ2 (ω2) receptors may be primarily involved in the convulsant action of PTZ. In the light/dark test, β-CCT abolished the anxiolytic-like action of diazepam. In tests designed to investigate the central depressant activity of drugs, β-CCT antagonized the sedative effects of diazepam and zolpidem, but failed to modify clearly the myorelaxant effects of diazepam. These differences may be related to the selectivity of β-CCT for BZ1 (ω1) sites as indicated by the preferential displacement of [3H]flumazenil in BZ1 (ω1)-enriched structures as compared to BZ2 (ω2)-enriched structures in the mouse. In in vitro experiments, β-CCT antagonized the potentiation of the GABA-induced Cl– current produced by zolpidem in HEK cells expressing the α1β2γ2 receptor or in cerebellar Purkinje neurones, while it failed to modify the diazepam potentiation at either α3β2γ2 or α5β3γ2 receptor subtypes. Conclusion: These results are consistent with the hypothesis that BZ1 (ω1) receptors play an important role in the anxiolytic and sedative/hypnotic effects of BZ (ω) receptor ligands, whereas activity at BZ2 (ω2) sites might be associated primarily with muscle relaxation.
    Materialart: Digitale Medien
    Bibliothek Standort Signatur Band/Heft/Jahr Verfügbarkeit
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  • 2
    ISSN: 1432-2072
    Schlagwort(e): Key words Anxiety ; Benzodiazepine ; Diazepam ; Elevated plus-maze ; Inbred and outbred mouse strains ; Light/dark test
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract  Rationale: Natural strain differences exist in mice for behavioural traits such as emotional reactivity. Objective: The present experiments compared the behavioural profiles of nine strains of mice (BALB/c, C57BL/6, C3H, CBA, DBA/2, NMRI, NZB, SJL, Swiss) in two models of anxiety after the administration of the benzodiazepine diazepam. Methods: The tests used were the light/dark choice task and the elevated plus-maze, two well-validated anxiolytic screening tests. Results: In vehicle-treated animals, differences on variables designed to measure anxiety-related behaviours were observed in both tests. In the light/dark test, the strains could be divided into three distinct groups: two non-reactive strains (NZB and SJL), an intermediate-reactive group (C3H, CBA, DBA/2, NMRI, C57BL/6 and Swiss), and one highly reactive strain (BALB/c). In the elevated plus-maze, SJL, NMRI, CBA and, to a lesser extent, C3H strains of mice, consistently showed low levels of anxiety-related behaviours. Intermediate levels were seen in the Swiss and BALB/c strains, and high levels of emotional reactivity were seen in C57BL/6, DBA/2 and NZB. The strain distribution between the light/dark and the elevated plus-maze tests shows similarities and differences, suggesting that each of these experimental procedures represents a different set of behaviours. Marked differences between a number of strains of mice in their sensitivity to the anxiolytic-like action of diazepam were observed in both the light/dark and the elevated plus-maze tests. Mice of the BALB/c, Swiss and, to a lesser extent, CBA and C3H strains were responsive to diazepam in both tests, although in the case of CBA mice, effects may have been contaminated by behavioural suppression. SJL mice were largely unresponsive to the action of the benzodiazepine in both tests, whereas in C57, DBA/2, NMRI and NZB mice, diazepam produced positive effects only in the elevated plus-maze. Conclusion: The finding of differential strain distributions both with and without diazepam treatment in the light/dark and the elevated plus-maze tests, indicates that not all strains of mice are suitable for investigating the effects of GABA/BZ receptor ligands. This study may thus provide a useful guide for choosing the best strain of mice for studying the pharmacology of fear-related behaviours.
    Materialart: Digitale Medien
    Bibliothek Standort Signatur Band/Heft/Jahr Verfügbarkeit
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