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 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.
Deransart
C
C
Klinikum der Albert-Ludwigs-Universität, Neurozentrum, Sektion Klinische Neuropharmakologie, Breisacherstr. 64, D-79106, Freiburg im Breisgau, Germany. deransar@nz11.uk1.uni-freiburg.de
Riban
V
V
Lê
B
B
Marescaux
C
C
Depaulis
A
A
D000818:Animals; D003342:Corpus Striatum / Q000187:drug effects*; D004298:Dopamine / Q000502:physiology*; D018491:Dopamine Agonists / Q000494:pharmacology*; D018492:Dopamine Antagonists / Q000494:pharmacology*; D004832:Epilepsy, Absence / Q000139:chemically induced / Q000188:drug therapy* / Q000503:physiopathology; D008297:Male; D009714:Nucleus Accumbens / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D013378:Substantia Nigra / Q000187:drug effects; D009435:Synaptic Transmission / Q000187:drug effects* / Q000502:physiology
D018491:Dopamine Agonists; D018492:Dopamine Antagonists; D004298:Dopamine