TOLERANCE TO THE ANXIOLYTIC EFFECTS OF THE TRIAZOLOBENZODIAZEPINES TRIAZOLAM AND ALPRAZOLAM, AS MEASURED BY THE INGESTION OF A HYPERTONIC SODIUM-CHLORIDE SOLUTION IN RATS

Rats were adapted to a water-deprivation regimen that allowed daily 1- hr drinking sessions of a single fluid, either 1.5% NaCl solution or w ater. Oral, presession, acute doses of triazolam (0.05-1.6 mg/kg) or a lprazolam (0.4-6.4 mg/kg) produced dose-related increases in session N aCl solution ingestion. The relative potencies found for these two dru gs approximated their relative K-i values reported in the literature. The increased ingestion produced in this and other experiments by anxi olytic agents is presented as an alternative way of evaluating punishm ent attenuation, and hence anxiolytic activity. Chronic oral dosing (e very 2nd day) with triazolam (0.2 mg/kg) or alprazolam (1.2 mg/kg) led , after several weeks, to partial, but surmountable, tolerance to the increased NaCl solution ingestion produced by these drugs, which was c onfirmed by a rightward shift in the dose-effect relations. During chr onic dosing, no corresponding declines in the independently evaluated increases in water intake produced by these drugs occurred. Abrupt dru g discontinuation produced a precipitous decrease in NaCl solution int ake, with subsequent recovery. For triazolam, the initial discontinuat ion decrease in intake to below the original base line suggested the p ossible accrual of a mild physiological dependence under this moderate chronic dose regimen.