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  • Acute and chronic treatments  (3)
  • Benzodiazepine  (2)
  • 1
    ISSN: 1432-2072
    Keywords: Cianopramine ; Citalopram ; 5-HT reuptake inhibitors ; Light/dark choice procedure ; Elevated plus-maze test ; Anxiety ; Neophobia ; Acute and chronic treatments
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract This study investigated behavioural effects of very potent 5-HT reuptake inhibitors after acute treatment (cianopramine and citalopram), as well as after chronic treatment (cianopramine), in two behavioural models of anxiety: 1) the light/dark choice procedure in mice and 2) the elevated plus-maze test in rats. In addition, the responses of mice to novelty in a free exploration paradigm were assessed after acute administration of both drugs. A single injection of cianopramine or citalopram increased neophobic reactions in the free exploration test. Furthermore, these drugs increased the avoidance reaction to a brightly illuminated chamber in the light/dark choice procedure as well as to open arms in the elevated plus-maze test. In contrast, after chronic treatment (10 mg/kg IP, once daily for 21 days) of cianopramine, anxiogenic-like effects were no longer produced in the light/dark choice paradigm whereas in the elevated plus-maze test, anxiolytic-like effects appeared. These results shed more light on the 5-HT hypothesis of anxiety, insofar as the increased availability of 5-HT resulting here from reuptake inhibition seems to initially result in an increased emotional reactivity which, however, subsequently disappears during chronic treatment.
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1432-2072
    Keywords: Key words Anxiety ; Benzodiazepine ; β-CCT ; BZ (ω) receptor ; Convulsions ; Diazepam ; In vivo binding ; Mice ; Myorelaxation ; Sedation ; Zolpidem
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: 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.
    Type of Medium: Electronic Resource
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  • 3
    ISSN: 1432-2072
    Keywords: Key words Befloxatone ; Moclobemide ; Reversible monoamine oxidase inhibitors ; Defensive behaviours ; Flight ; Risk assessment ; Panic ; Anxiety ; Acute and chronic treatments ; Swiss mouse
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The present study compared the behavioural effects of acute and chronic (one daily IP injection for 14 days) treatments with the reversible monoamine oxidase-A inhibitors (RIMAs) moclobemide (3 and 10 mg/kg) and befloxatone (0.3 and 1 mg/kg) in the Mouse Defence Test Battery (MDTB) which has been designed for screening anxiolytic and anti-panic drugs. In the MDTB, Swiss mice were confronted with a natural threat (a rat) and situations associated with this threat. Primary measures taken before, during and after rat confrontation were escape attempts, flight, risk assessment (RA) and defensive threat and attack. After acute administration of both compounds, no modification of defensive behaviours were observed. This was in contrast to chronic treatments, where moclobemide (3 and 10 mg/kg) and befloxatone (1 mg/kg) produced a significant reduction in one flight measure (avoidance distance when the rat was approaching). In addition, befloxatone (0.3 and 1 mg/kg), but not moclobemide, increased RA responses when mice were constrained in one part of the apparatus facing the rat, which remained at a constant distance. No other drug effects were observed with either compound. Although these behavioural profiles are consistent with an anxiolytic-like effect, the finding of an action upon a limited number of defence responses suggests a weaker anxiolytic-like potential compared to that of classical anxiolytics. However, in view of previous data with panic-modulating compounds on flight behaviours in the MDTB, the present results are in line with clinical results showing that moclobemide is effective in panic disorders and suggest that befloxatone may have some efficacy in the clinical management of panic.
    Type of Medium: Electronic Resource
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  • 4
    ISSN: 1432-2072
    Keywords: Imipramine ; Fluoxetine ; 5-HT reuptake inhibitors ; Flight ; Antipredator defense ; Fear ; Anxiety ; Panic ; Predator assessment ; Acute and chronic treatments ; Swiss-Webster mouse
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The Mouse Defense Test Battery (MDTB) has been designed to assess defensive reactions in Swiss-Webster mice to situations associated with a natural predator, the rat. Primary measures taken before, during and after predator confrontation comprise escape attempts, predator assessment, defensive attack and flight. Previous reports from this laboratory have shown that the panic-promoting drug yohimbine potentiated flight behavior, while long-term treatment with the panicolytic agent alprazolam reduced this response. In order to evaluate further the possibility that the MDTB may represent an effective animal model of panic attacks, the present study investigated the behavioral effect of imipramine and fluoxetine, two serotonin reuptake inhibitors (SRIs) known to alleviate panic symptoms when given on a repeated basis. Both drugs were administered acutely and chronically (one daily IP injection for 21 days) at 5, 10 and 15 mg/kg. Our results showed that a single dose of imipramine or fluoxetine strongly potentiated flight reactions in response to an approaching predator and increased defensive attack toward the rat. This was in contrast to chronic treatment with each drug which dramatically decreased flight responses and defensive attack behaviors. In addition, long-term administration with both SRIs produced a reliable attenuation of predator assessment activities. Taken together, these findings suggest an acute anxiogenic-like effect of imipramine and fluoxetine followed by a fear/anxiety reducing effect after repeated administrations. These results support clinical observations revealing an acute anxiogenic effect of SRIs followed by an anxiolytic and/or panicolytic effect after chronic use, and support previous results suggesting that the MDTB may be useful for the investigation of panic-modulating agents.
    Type of Medium: Electronic Resource
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  • 5
    ISSN: 1432-2072
    Keywords: Key words Anxiety ; Benzodiazepine ; Diazepam ; Elevated plus-maze ; Inbred and outbred mouse strains ; Light/dark test
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: 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.
    Type of Medium: Electronic Resource
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