Midazolam withdrawal and discriminative motor control: effects of FG 7142 and Ro 15-1788.

Rats chronically drank either water or midazolam solution (0.1 mg/ml) in daily, 3-h schedule-induced polydipsia sessions and were evaluated in daily motor control sessions after polydipsia when midazolam metabolite levels had fallen to zero (withdrawal). Under midazolam polydipsia, animals orally self-administered between 21 and 38 mg/kg daily. The effect of acute drug administration [midazolam (0.75-3 mg/kg, SC), FG 7142 (1-8 mg/kg, IP), Ro 15-1788 (10-20 mg/kg, IP)] on motor control performance was similar after either chronic water or midazolam polydipsia. Thus chronic, oral midazolam self-administration did not lead to tolerance to the motor impairment produced by SC midazolam, nor did the daily discontinuation lead to impaired motor performance, nor had these performances, which occurred after daily elevated midazolam metabolite levels had reached zero (withdrawal), become sensitized to the effects of either the benzodiazepine inverse agonist FG 7142 or the agonist Ro 15-1788.