Effects of benzodiazepine administration on A1 adenosine receptor binding in-vivo and ex-vivo.

The adenosine receptor has been implicated in the central mechanism of action of benzodiazepines. The specific binding of an A1-selective adenosine antagonist radioligand, [3H]8-cyclopentyl-1,3-dipropylxanthine, was measured in-vivo in mice treated with alprazolam (2 mg kg-1, i.p.), lorazepam (2 mg kg-1, i.p.) and vehicle. Binding studies were performed in-vivo and ex-vivo in mice receiving continuous infusion of alprazolam (2 mg kg-1 day-1), lorazepam (2 mg kg-1 day-1) and vehicle by mini-osmotic pumps for 6 days. Continuous infusion of alprazolam and lorazepam significantly decreased specific binding by 34 and 53%, respectively, compared with vehicle treatment (P less than 0.01). Single doses of alprazolam and lorazepam induced a similar trend in specific binding in-vivo (P = 0.07). There were no alterations in A1-receptor density (Bmax) or affinity (Kd) in cortex, hippocampus or brainstem in ex-vivo studies. Benzodiazepine treatment may diminish A1- receptor binding in-vivo by inhibiting adenosine uptake or by direct occupancy of the A1 adenosine receptor recognition site.