Concurrent treatment with verapamil prevents diazepam withdrawal-induced anxiety, in the absence of altered calcium flux in cortical synaptosomes.

Rats, chronically treated with diazepam (4 mg/kg/day) for 28 days, displayed increased anxiety when tested in the elevated plus-maze, 42 hr after the last dose. This anxiogenic withdrawal response was entirely prevented by the concurrent administration of the calcium channel antagonist, verapamil. No anxiolytic effect of chronic administration of verapamil was observed in vehicle-treated rats. To investigate the possibility that increased calcium function in nerve terminals might underlie diazepam withdrawal-induced anxiety, the uptake by cortical synaptosomes of 45Ca2+ was studied. Both fast (3-sec) and slow (60-sec) phase uptake were measured. No changes in basal (5 mM), potassium-stimulated (55 mM) or net uptake were observed during either fast or slow phase uptake. It is concluded that increased calcium influx in nerve terminals in the cortex does not underlie the anxiogenic effect of withdrawal of the benzodiazepine but that further studies must be carried out in other regions of the brain.