Calcium channel agonists and dystonia in the mouse

Systemic administration of the L-type calcium channel agonists +/-Bay K 864 4 or FPL 64176 causes a characteristic pattern of motor dysfunction in norm al C57BL/6J mice that resembles generalized dystonia. There is no associate d change in the electroencephalogram, confirming that the motor disorder do es not reflect epileptic seizures. However, the electromyogram reveals an i ncrease in baseline motor unit activity with prolonged phasic discharges co nsistent with dystonia. The duration and severity of dystonia is dependent on the dose administered and the age of the animal at testing. The effects are transient, with the return of normal motor behavior 1-4 hours after tre atment. Similar effects can be provoked by intracerebral administration of small amounts of the drugs, indicating a centrally mediated response. Dysto nia can be attenuated by co-administration of dihydropyridine L-type calciu m channel antagonists (nifedipine, nimodipine, and nitrendipine) but not by non-dihydropyridine antagonists (diltiazem, verapamil, and flunarizine). T hese results implicate abnormal function of L-type calcium channels in the expression of dystonia in this model.