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Microgram doses of diazepam do not induce proconvulsant or proconflict effects in rodents
M H Thiébot1, A M Laporte, P Soubrié
1INSERM - U 302, Département de Pharmacologie, Faculté de Médecine Pitié-Salpêtrière, Paris, France.
Abstract:
Cooper (1983, 1985) observed an inhibition of ambulation and fluid intake in rats following diazepam in the microgram dose range. The present study aimed at investigating the effects of microgram doses of this benzodiazepine on i) the threshold doses of either pentylenetetrazole, picrotoxin or bicuculline required to induce seizures in mice and ii) the suppression of lever pressing for food induced by the delivery of one electric footshock every ten presses in rats pretreated or not with isoniazid (64 mg/kg IP). Diazepam 4-32 micrograms/kg IP) neither reduced seizure threshold doses of either convulsant studied nor did this drug (16-128 micrograms/kg IP) reliably decrease the number of lever presses under the punishment schedule. The present study provides no further evidence for a dose-related biphasic effect of diazepam which could give new insight into the functioning of benzodiazepine-coupled brain processes.
Insights
This study found that low microgram doses of diazepam did not alter seizure thresholds in mice or suppress punished lever pressing in rats. These findings do not support a dose-related biphasic effect of diazepam in the central nervous system.
Area of Science:
- Neuropharmacology
- Behavioral Neuroscience
Background:
- Previous research indicated diazepam at microgram doses inhibited rat ambulation and fluid intake.
- The existence of a dose-related biphasic effect of diazepam remains an area of investigation.
Purpose of the Study:
- To investigate the effects of microgram diazepam doses on seizure thresholds induced by convulsants.
- To examine diazepam's impact on punished operant behavior in rats.
Main Methods:
- Mice were administered diazepam (4-32 µg/kg) and convulsant thresholds (pentylenetetrazole, picrotoxin, bicuculline) were assessed.
- Rats were treated with isoniazid and subjected to a punishment schedule (footshock) while receiving diazepam (16-128 µg/kg).
Main Results:
- Diazepam did not significantly alter the seizure threshold doses for any of the tested convulsants.
- Diazepam did not reliably decrease lever pressing under the punishment schedule in rats.
Conclusions:
- The study found no evidence supporting a dose-related biphasic effect of microgram diazepam doses.
- Further research is needed to understand the precise functioning of benzodiazepine-coupled brain processes at low doses.