Chlordiazepoxide and valproate enhancement of saline drinking by nondeprived rats: effects of bicuculline, picrotoxin and Ro15-1788.

Drinking of 0.85% saline by nondeprived rats was significantly enhanced by chlordiazepoxide (5 or 10 mg/kg) and by valproate (100 or 300 mg/kg), drug effects being strongest in the earlier parts of a 30-minute test. When given alone, both bicuculline and picrotoxin significantly reduced saline drinking at 2.5 mg/kg, but not 1.5 mg/kg. Administration of valproate at either dose or of chlordiazepoxide (10 mg/kg) completely prevented bicuculline action and 5 mg/kg chlordiazepoxide reduced it. Picrotoxin, however, largely prevented the actions of both chlordiazepoxide and valproate. The increase in saline drinking induced by valproate (300 mg/kg) was also blocked by RO15-1788 (10 or 25 mg/kg). These findings are discussed in the context of the three-site model of the GABA/benzodiazepine receptor complex. It is concluded that drugs acting at the benzodiazepine site or the chloride ion channel affect saline drinking, but that there is little evidence of an important functional role for the GABAa site at present.