Pentobarbital blocks the pentylenetetrazole‐like effect of withdrawal from chronic diazepam

Rats trained to detect the stimulus properties of an anxiogenic drug, pentylenetetrazole (PTZ), substitute preciptated withdrawal from chronic administration of diazepam (DZP) for the PTZ stimulus. The present studies tested pentobarbital (PB), ethanol (ETOH), and clonidine (CL) for their ability to block this withdrawal stimulus. Rats were trained to discriminate PTZ (20 mg/kg) in a two‐lever choice task. Prior to chronic administration of DZP, the benzodiazepine (BDZ) antagonist Ro 15‐1788 (0.64–320 mg/kg) did not substitute for PTZ. PB blocked PTZ in a dose‐related manner, but ETOH and CL did not. Following these tests, rats were given DZP (20 mg/kg, ip) every 8 hr for 10 days. On days 7–10 of this regimen, they were tested for substitution of the PTZ stimulus by Ro 15‐1788 (10 mg/kg) and for blockade of this substitution by PB, ETOH, or CL. Ro 15‐1788 substituted fully for PTZ, and this substitution was blocked by PB but not by ETOH and CL. These data parallel recent reports from human studies that CL is ineffective in treating BDZ withdrawal, and they suggest that discrimination of PTZ may have utility for investigating treatments that will suppress the subjective aspect of BDZ withdrawal.