Cooper (1983
Cooper ( , 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 gg/kg IP) neither reduced seizure threshold doses of either convulsant studied nor did this drug (16-128 pg/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.
Key words. Microgram doses of diazepam -Convulsions -Punishment-induced behavioral suppression -Mouse -Rat
For various neurotransmitter systems, there is evidence that low and high doses of the same drug can affect neural activity differentially and thus lead to the induction of opposite behavioral changes. For example, the drug may act preferentially at autoreceptors or postsynaptic receptors, depending upon the dose. Recent data tend to indicate that this could also be the case for benzodiazepines. Indeed, Cooper (1983, 1985) reported that, in rats, a microgram dose of diazepam decreased ambulation and fluid intake, whereas it is well documented that usual anti-anxiety doses (milligram range) of this drug enhance exploratory behavior and flood or fluid consumption (see: Thi6bot and Soubri6 1983;Treit 1985). Given the attractive speculations that Cooper's observations might generate concerning benzodiazepin-sensitive brain processes (putative tonically active endogenous ligand(s) and benzodiazepine autoreceptors), the present study aimed at investigating whether microgram doses of diazepam may have proconvulsant activity in mice and °° anxiogenic" (proconflict) effects in rats. In addition, the effects of a selective blockade of benzodiazepine-related systems might be more easily detected when ?~-aminobutyric acid (GABA) transmission is reduced. Indeed, the benzodiazepine-receptor antagonist Ro 15-1788 has been de-