Sustained synergism by chronic caffeine of the motor control deficit produced by midazolam

To evaluate the effects of chronic caffeine on the impairment of discriminative fine motor control produced by midazolam, rats were trained to hold a force transducer steady to deliver food pellets. Chronic, daily doses of midazolam (3 mg/kg SC) led to a stable level of motor impairment. Chronic caffeine (20 mg/kg IP) alone usually produced a more moderate deficit or, for one animal, no deficit. Combined, chronic administration of these doses yielded a sustained synergism in motor performance impairment, which contrasted with the antagonism usually found between the benzodiazepines and methylxanthines when performance is evaluated by psychomotor tests not requiring fine motor control. The observed synergism was not explicable in terms of measured disposition of the drugs. The synergistic production of fine motor dyskinesia by the concurrent administration of caffeine and midazolam may be relevant to the triggering of anxiety attacks by caffeine observed in panic disorder patients.