CGS 9896, a pyrazoloquinoline that potently binds to
benzodiazepine receptors, has been reported to have anticonflict activity in conventional footshock paradigms and to antagonize
pentylenetetrazol-induced
seizures. In the present experiments, the
pentylenetetrazol discriminative cue was blocked by
CGS 9896 with a potency comparable to that of
diazepam.
CGS 9896 also selectively lengthened the latency to terminate self-initiated brain stimulation reward. These procedures extend the
anxiolytic activity of
CGS 9896 to models that do not rely upon footshock-induced conflict.
CGS 9896 did not impair the
traction reflex in mice, did not impair rotorod performance in rats, did not reduce unpunished operant responding and decreased motor activity only slightly, indicating no distinguishable sedation or muscle relaxation in rodent models. In fact,
diazepam-induced rotorod impairment was blocked by
CGS 9896. The
anticonvulsant effects of
CGS 9896, as indicated by audiogenic seizure and
pentylenetetrazol-induced seizure studies, were substantial but were weaker than those of
diazepam, possibly because of the muscle relaxant component of
diazepam.
Ethanol-induced motor impairment was potentiated more markedly by
diazepam than by
CGS 9896. Mixed agonist-antagonist properties of
CGS 9896 therefore emerge when a comprehensive battery of behavioral assessments is utilized.
CGS 9896 may have clinical
anxiolytic activity without sedation or muscle relaxation.