Noradrenergic influences on sound-induced seizures

The preferential alpha-2 noradrenergic agonists, clonidine (0.2--0.4 mg/kg), oxymetazoline (2.5--10.0 mg/kg) and UK 14,304 (0.6 mg/kg), when given i.p., reduce the severity of audiogenic seizures in 19- to 26-day-old DBA/2 mice. This protective effect can be diminished or reversed by alpha-2 noradrenergic antagonists such as yohimbine (2.5 mg/kg) or piperoxan (20--50 mg/kg) given i.p. or phentoalamine (100 micrograms) given intracerebroventricularly. It is not reversed by the preferential alpha-1 noradrenergic antagonist phenoxybenzamine (5 mg/kg) given i.p. Yohimbine, (1--2.5 mg/kg), piperoxan (20--50 mg/kg) or phenoxybenzamine (5 mg/kg) given i.p. alone did not change the severity of audiogenic seizure responses. Phentolamine (10--100 micrograms) or prazosin (10--50 micrograms) given intracerebroventricularly induced spontaneous limb myoclonus in some mice. Audiogenic seizure responses were unchanged after phentolamine (10--100 micrograms) but were reduced after prazosin (25--50 micrograms). Activation of a receptor pharmacologically similar to the peripheral alpha-2 noradrenergic receptor protects against seizures in this epilepsy model.