Inhibition of the substantia nigra pars reticulata has been shown to suppress
seizures in different animal models of
epilepsy. The striatum is the main input of the substantia nigra pars reticulata. The aim of the present study was to examine the role of dopaminergic neurotransmission within the striatum in the control of absence
seizures in a genetic model in the rat.
Injections of mixed dopaminergic D1/D2 or of selective D1 or D2 agonists or antagonists in the dorsal parts of the striatum led to suppression of absence
seizures associated with strong behavioral and electroencephalographic side-effects. When injected in the ventral part of the striatum (i.e. the nucleus accumbens core), all these agonists and antagonists respectively decreased and increased absence
seizures without behavioral or electroencephalographic side-effects. Combined
injections of low doses of a D1 and a D2 agonist in the core of the nucleus accumbens had an additive effect in absence
seizures suppression. Furthermore, combined
injections of low doses of a
GABA(A) agonist and a
N-methyl-D-aspartate antagonist in the substantia nigra also had cumulative effects in absence
seizures suppression. These results show that
dopamine neurotransmission in the core of the nucleus 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 involved in the modulation of absence
seizures.