Potentiation of amygdaloid kindling and metrazol-induced seizures by 6-hydroxydopamine in rats

Intact control rats and rats pretreated with an intraventricular injection of 6-hydroxydopamine (6-0HDA) received a convulsive dose of pentylenetetrazol (Metrazol). The control rats responded to the subcutaneous injection of Metrazol with one or more brief intermittent clonic convulsions. In contrast, the rats pretreated with 6-OHDA displayed significantly longer episodes of generalized seizures, nearly all of which contained episodes of tonic extension of the hindlimbs. The severity of the seizure syndrome in rats with substantial depletion of both norepinephrine (NE) and dopamine (DA) did not differ markedly from that in rats with preferential depletion of NE, suggesting that depletion of NE and not DA is the mechanism of the exacerbated convulsive response to Metrazol produced by 6-OHDA. In a second experiment, intact and 6-OHDA-treated rats were subjected to a kindling procedure, wherein daily electrical stimulation of the amygdala that was initially subconvulsive eventually came to elicit bilateral clonic convulsions. Rats with substantial depletion of both NE and DA required less than half as many stimulations to kindle seizures as did intact rats or rats with preferential depletion of NE, and they continued to display significantly longer afterdischarges for nearly 15 days after the first kindled seizure. These data suggest that combined destruction of noradrenergic and dopaminergic neurons, or destruction of the latter alone, is necessary to facilitate the development of kindled seizures. Together, the two experiments confirm earlier observations that central catecholaminergic systems tend to inhibit a variety of seizure phenomena.