Conditional attenuation of the antipentylenetetrazol activity of chlordiazepoxide.

In a study of drug-drug conditioning, chlordiazepoxide (CDP) was administered to rats 30 min before chlorpromazine (CPZ) every 3-4 days for 5 weeks. Thereafter, CDP was tested for its ability to a) increase animals' exploration of the normally avoided "exposed" arms of a plus-maze (a screening method for anxiolytic substances) and b) protect against seizures induced by pentylenetetrazol (PTZ). The CDP-CPZ conditioning procedure potentiated the usual increase in open-arm activity seen in CDP-injected rats but attenuated the anti-PTZ effect. When injected with CDP 60 min prior to PTZ, rats with a previous history of CDP-CPZ pairings had shorter latencies to seizure onset and showed a greater likelihood of progression to the most severe behavioral indices of a maximal seizure relative to control subjects with a history of backward drug pairings (CPZ-CDP) or pairings of CDP with isotonic saline.