Dopamine in the striatum modulates seizures in a genetic model of absence epilepsy in the rat

Inhibition of the substantia nigra pars reticulata has been shown to suppre ss seizures in different animal models of epilepsy. The striatum is the mai n input of the substantia nigra pars reticulata. The aim of the present stu dy was to examine the role of dopaminergic neurotransmission within the str iatum in the control of absence seizures in a genetic model in the rat. Inj ections of mixed dopaminergic D1/D2 or of selective D1 or D2 agonists or an tagonists in the dorsal parts of the striatum led to suppression of absence seizures associated with strong behavioral and electroencephalographic sid e-effects. When injected in the ventral part of the striatum (i.e. the nucl eus accumbens core), all these agonists and antagonists respectively decrea sed and increased absence seizures without behavioral or electroencephalogr aphic side-effects. Combined injections of low doses of a D1 and a D2 agoni st in the core of the nucleus accumbens had an additive effect in absence s eizures suppression. Furthermore, combined injections of low doses of a GAB AA agonist and a N-methyl-D-aspartate antagonist in the substantia nigra al so had cumulative effects in absence seizures suppression. These results show that dopamine neurotransmission in the core of the nucle us accumbens is critical in the control of absence seizures. The modulatory and additive effects on absence seizures of dopaminergic neurotransmission through both the D1 and D2 receptors in the core of the nucleus accumbens further suggest that ventral pathways of the basal ganglia system are invol ved in the modulation of absence seizures. (C) 2000 IBRO. Published by Else vier Science Ltd. ALI rights reserved.