ISSN:
1432-2072
Keywords:
Key words Xanthine drug
;
Caffeine
;
Pentoxifylline
;
Diazepam
;
Hole-board
;
Head dip
Source:
Springer Online Journal Archives 1860-2000
Topics:
Medicine
Notes:
Abstract Rationale: The behavioral effects of methyl xanthines and their interactions with benzodiazepines have not been clearly established in animal models of anxiety. Objective: The present study extended the previous studies to determine the effects of acute and repeated administration of caffeine, a non-specific phosphodiesterase (PDE) inhibitor and pentoxyfylline, a specific type-4 phosphodiesterase (PDE4) inhibitor on (1) baseline anxiety-like behavior and (2) the response to an acute challenge with diazepam on anxiety-like behavior in the hole-board test. Methods: Mice were observed for the number of head-dips they made into the holes of the hole-board apparatus during a 5-min period, starting 30 min after acute (20 mg/kg) and repeated oral dose (20 mg/kg, twice a day for 4 days) administration of caffeine and pentoxifylline. In separate experiments, the response to an acute challenge with graded doses of diazepam (0.375–3 mg/kg, SC) was observed in naive mice or mice on acute and repeated dose regimen with methyl xanthines. Results: Mice on acute but not after repeated dose regimen demonstrated a significantly increased number of hole-dips, indicating an anxiolytic-like effect of methylxanthines. Diazepam at the lower doses (0.375 and 0.75 mg/kg) but not at the highest doses (1.5 and 3 mg/kg) examined produced a significant anxiolytic-like effect. After an acute dose exposure of mice to caffeine and pentoxifylline, a rightward shift in the dose-response curve of diazepam was observed and particularly at 1.5 mg/kg dose, the net effect of diazepam was significantly enhanced which was, however, impaired upon repeated administration, more so with caffeine than with pentoxifylline. Conclusions: It is concluded that the xanthine drugs exert anxiolytic-like activity similar to diazepam in the hole-board test. In addition, they seem to modulate the anxiolytic effects of diazepam after both acute and repeated administration, probably as a result of an endogenous adenosinergic mechanism which may have therapeutic significance.
Type of Medium:
Electronic Resource
URL:
http://dx.doi.org/10.1007/s002130050977
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