Neuropharmacological evidence for an interaction between the GABA uptake inhibitor Cl‐966 and anxiolytic benzodiazepines

[1‐[2‐[bis(trifluoromethyl)‐phenyl]methoxy]ethyl]‐ 1,2,5,6‐tetrahydro‐3‐pyridine‐carboxylic acid, HCl (Cl‐966, Parke‐Davis) is a new specific inhibitor of GABA uptake to neurons that is severalfold more potent than for inhibition of glycine or glutamate uptake. Cl‐966 crosses the blood‐brain barrier and when injected intravenously into rats (doses up to 10.5 μM/Kg = 5.0 mg/kg) produces only marginal behavioral effects. Cl‐966 also produces a modest reversal of punished‐suppressed drinking behavior in thristy rats both in the conflict and phenylenetetrazole (PTZ)‐induced proconflict Vogel test. However an inactive dose of Cl‐966 (6.3 μM/kg i.v., 90 min prior to the test) significantly potentiated the anticonflict and anti‐PTC‐induced proconflict action of diazepam and alprazolam. The anticonflict/antiproconflict ED50 ratio for diazepam was shifted from 1.2 to 1.0 and that of alprazolam from 13.0 to 7.0 after pretreatment with Cl‐966.

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