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  • 5-HT Antagonists  (1)
  • Glycine/NMDA receptor  (1)
  • Locomotor activity  (1)
  • 1
    ISSN: 1432-2072
    Keywords: R04-4602 ; 5-HT Antagonists ; Activity ; Tryptophan
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract l-Tryptophan at moderately low dosage (20 mg/kg) reduced the activity of rats taken during a dark period (red light) and put into an open field illuminated by bright white light. Activity was not altered when the field was illuminated by red light. Tryptophan did not cause significant hypoactivity in rats pretreated with the 5-hydroxytryptamine (5-HT) receptor antagonists methysergide, cyproheptadine and metergoline. However, tryptophan did not alter brain 5-HT concentration and only increased 5-hydroxyindoleacetic acid (5-HIAA) slightly in rats killed shortly after behavioural observation. A further indication that the behavioural effect of tryptophan was not due to increased brain 5-HT was its prevention by R04-4602 at a dose sufficient to block peripheral but not central l-aromatic amino acid decarboxylase. The results suggest that the above behavioural effect of l-tryptophan is peripherally mediated. A number of potential mechanism are discussed.
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1432-2072
    Keywords: Elevated plus maze ; Anxiety ; Chlordiazepoxide hydrochloride ; d-Amphetamine sulphate ; FG 7142 ; Buspirone ; Locomotor activity ; Rats
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract In exploratory animal models of anxiety, such as the elevated plus maze, the anxiogenic- and anxiolytic-like effects of drugs may be confounded by changes in locomotor activity. In the present experiments, the sensitivity of several measures of anxiety and locomotor activity in the elevated plus maze were assessed. Both chlordiazepoxide hydrochloride (CDP, 7.5 mg/kg) andd-amphetamine sulphate (AMP, 0.75, 1.5 mg/kg) increased the percent time on the open arms and doses of 7.5 mg/kg and 1.5 mg/kg CDP and AMP, respectively, increased the number of entries into the open arms. The increase in these measures might suggest that both compounds induced an anxiolytic-like effect. Although FG 7142 (30.0 mg/kg) did not decrease the number of entries to the open arms, it did decrease the time on the open arms, which might suggest that it had anxiogenic-like effects. Similarly, buspirone reduced both the number of entries into the open arms and the time spent on the open arms. However, all the compounds significantly affected locomotor activity. CDP (3.0 and 7.5 mg/kg) increased the total number of arm entries, the distance travelled on the open arms and the mean speed of the animals on the open, and in the closed arms. Moreover, the distance travelled by the animals in the closed arms was increased by 1.0 mg/kg CDP, a dose that had no measurable effects on the indices of anxiety. Similarly, although AMP failed to increase the total number of arm entries, it did increase the distance travelled in the closed arms (0.75 and 1.5 mg/kg), on the open arms (1.5 mg/kg) and the speed of the animals in the closed arms (1.5 mg/kg), a measure that is independent of the time spent in the closed arms. By contrast, both FG 7142 (30.0 mg/kg) and buspirone decreased the total number of arm entries (0.3–8.0 mg/kg), the speed of the animals in the closed arms and the distance travelled in the closed arms (1.0–4.0 mg/kg). These experiments suggest that: (i) the anxiogenic- and anxiolytic-like effects of drugs in the elevated plus-maze are confounded by changes in locomotor activity and that “total arm entries” is a relatively insensitive measure of drug-induced changes in locmotor activity; (ii) psychostimulant compounds, such as AMP, at doses that increase locomotor activity have an anxiolytic-like profile in the elevated plus maze and (iii) the measurement of speed of movement is a more sensitive index of changes in locmotor activity than the conventional measure of “total arm entries”.
    Type of Medium: Electronic Resource
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  • 3
    ISSN: 1432-2072
    Keywords: Prepulse inhibition ; Acoustic startle Social isolation ; Glycine/NMDA receptor ; L-701,324 Dopaminergic hyperactivity
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Previous studies have demonstrated that the glycine/NMDA receptor antagonist, L-701,324 (7-chloro-4-hydroxy-3(3-phenoxy)phenyl-2(H)quinolone) blocks the activation of mesolimbic dopamine systems induced following psychostimulant administration in the rat (Bristow et al. 1994). In the present study, pretreatment with L-701,324 also reversed the deficit in prepulse inhibition (PPI) observed in rats reared in social isolation after weaning. Given that PPI is also attenuated in schizophrenic patients and that isolation rearing induces both neurochemical and behavioural abnormalities suggestive of a physiologically induced state of dopaminergic hyperactivity, these results suggest that blockade of the glycine/NMDA receptor may offer a new strategy for the development of novel antipsychotic agents.
    Type of Medium: Electronic Resource
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