Discriminative stimulus properties of the benzodiazepine receptor partial agonist beta-carbolines abecarnil and ZK 95962: a comparison with chlordiazepoxide.
Separate groups of rats were trained to discriminate one of three benzodiazepine receptor ligands from vehicle. The three ligands used, the benzodiazepine chlordiazepoxide, and the beta-carboline partial agonists ZK 95962 and abecarnil, have been reported to have different agonistic profiles. All three ligands formed specific benzodiazepine-receptor mediated discriminative stimuli antagonizable by at least one benzodiazepine antagonist. Different patterns of generalization were observed for each cue. As reported previously full and partial agonists substituted for chlordiazepoxide, whereas generalization to ZK 95962 was obtained more readily with partial agonists and antagonists with weak partial agonist activity. In contrast to the other two cues, the abecarnil discriminative stimulus was difficult to train and was unstable over time. Additionally, the abecarnil cue showed commonalities only with sedative or BZ1 receptor agonists. These results demonstrate qualitative differences between different benzodiazepine receptor ligands dependent on the intrinsic activity of the compound used.
Research Laboratories, Schering AG, Berlin, Germany.
J.S.
JS
Andrews
D.N.
DN
Stephens