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  • 1
    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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  • 2
    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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  • 3
    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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  • 4
    ISSN: 1432-2072
    Keywords: Benzodiazepines ; BZ-1 (ω 1) receptor ; Anxiety ; Elevated plus-maze ; Risk assessment ; Locomotor activity ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The behavioral effects of a wide range of BZ (ω) receptor ligands, including non-selective full (alprazolam, clorazepate, chlordiazepoxide and diazepam) and partial (bretazenil, imidazenil and Ro 19-8022) agonists, and selective BZ-1 (ω 1) (abecarnil, CL 218,872, CL 284,846 and zolpidem) receptor ligands, were compared in the rat elevated plus-maze test. Behaviors recorded comprised the traditional indices of anxiety as well as a number of ethologically derived measures. In addition, the specificity of drug effects was evaluated by measuring spontaneous locomotor activity in activity cages in separate groups of animals. Results showed that all compounds tested not only increased the proportion of time spent and proportion of entries into the open arms of the maze (considered as traditional indices of anxiety) but also affected headdippings and attempts at entry into open arms, which can be considered as indices of risk assessment responses. However, the magnitude of these effects was generally smaller with the BZ-1 (ω 1) selective agents. Moreover, additional differences were apparent on the total number of arm entries measure, which was significantly increased by most full and all partial agonists, but was unaffected by the selective BZ-1 (ω 1) compounds. If it is assumed that total arm entries are contaminated by anxiety, the latter finding indicates a weaker anxiety-reducing potential of selective BZ-1 (ω 1) ligands. Importantly, the increase in total arm entries induced by the non-selective agents was not associated with a similar effect on locomotion as revealed in the actimeter. Finally, anxiolysis produced by the BZ-1 (ω 1) ligands was invariably observed at doses which reduced locomotor activity, suggesting that the anxiolytic-like effects of these compounds are confounded by decreases in locomotor activity.
    Type of Medium: Electronic Resource
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  • 5
    ISSN: 1432-2072
    Keywords: CGS 15943A ; DPCPX ; Adenosine antagonists A1 and A2 ; Locomotion ; Anxiety
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract CGS 15943A is the first reported nonxanthine adenosine antagonist and it shows high affinity towards A1 and A2 receptors. The present data show that CGS 15943A increased in a dose-dependent manner locomotor activity of mice confronted with a free exploratory test without markedly modifying rears or, at low or medium doses, novelty seeking responses. In the light/dark choice procedure, which is especially appropriate for revealing anxiolytic and anxiogenic drug-effects, CGS 15943A decreased the time spent by mice in the lit box and increased the number of transitions. By contrast, the highly selective adenosine A1 receptor, DPCPX, did not significantly modify the behavior of mice except at high doses, which decreased it in the free exploratory test. It is suggested that the present findings confirm the hypothesis that the behavioral effects of adenosine antagonists are linked to their actions at adenosine A2 receptors.
    Type of Medium: Electronic Resource
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  • 6
    ISSN: 1432-2072
    Keywords: Fluprazine ; Eltoprazine ; Serenics ; Exploration ; Locomotion ; Rearing ; Light/dark procedure ; Anxiety ; Emotionality ; Mice
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Two tests designed to elicit responses to novelty and to aversive stimuli were used to study the effects of the serenics fluprazine and eltoprazine on the behaviour of male Swiss mice: a free exploratory test (fluprazine: 2.5, 5 and 10 mg/kg; eltoprazine: 2.5, 5, 10 and 15 mg/kg) and a two-box choice procedure (fluprazine: 1.25, 2.5, 5 and 7.5 mg/kg; eltoprazine: 2.5, 5, 7.5 and 10 mg/kg). Both drugs increased the neophobic reaction, as well as the avoidance of a brightly illuminated box. These effects closely resemble those of psychostimulant drugs such as methamphetamine and caffeine. It is hypothesized that the behavioural changes induced by these drugs may be due to a nonspecific increase of the emotional reactivity of animals.
    Type of Medium: Electronic Resource
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