Anticonvulsant effect of striatal dopamine D2 receptor stimulation: dependence on cortical circuits?
In the pilocarpine model of epilepsy, dopamine can either inhibit (via D2 receptors) or facilitate (via D1 receptors) the spread of limbic motor seizures. The anticonvulsant action of D2 receptor activation has been localized to the anterior striatum, but disappears if excessive damage is caused to the overlying cerebral cortex. This study examines the possibility that the corticostriatal projection is involved in the anticonvulsant response to striatal D2 receptor stimulation, by comparing the seizure-protecting efficacy of intrastriatal trans-(+)-4,4a,5,6,7,8,8a,9-octahydro-5-propyl-2H-pyrazolo-(3,4-g)quinol ine hydrochloride (LY 171555) in control rats, and in rats bearing discrete bilateral kainic acid lesions of the cerebral cortex. The results show that neurotoxin injection induces a punctate lesion of the primary motor area of the cortex in each hemisphere, with no injury to the underlying caudate-putamen, or to more distant structures such as the hippocampus. The lesion, however, was sufficient to abolish the protective effect of intrastriatal LY 171555 against pilocarpine challenge. To explain these findings, an interplay between nigrostriatal dopaminergic and corticostriatal glutamatergic neurons is proposed, in which the anticonvulsant tendency of the excitatory amino acid is accentuated by dopamine, probably by acting on D2 receptors which facilitate the release of glutamate from axon terminals.
Department of Pharmacology, School of Pharmacy, London, U.K.
G
G
al-Tajir
M S
MS
Starr
D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology*; D002540:Cerebral Cortex / Q000502:physiology*; D003342:Corpus Striatum; D015259:Dopamine Agents / Q000494:pharmacology; D004873:Ergolines / Q000008:administration & dosage / Q000494:pharmacology; D005260:Female; D007608:Kainic Acid; D008297:Male; D009044:Motor Cortex; D010862:Pilocarpine; D019257:Quinpirole; D051381:Rats; D011919:Rats, Inbred Strains; D011954:Receptors, Dopamine / Q000187:drug effects*; D017448:Receptors, Dopamine D2; D012640:Seizures / Q000139:chemically induced; D013238:Stereotaxic Techniques
D000927:Anticonvulsants; D015259:Dopamine Agents; D004873:Ergolines; D011954:Receptors, Dopamine; D017448:Receptors, Dopamine D2; D010862:Pilocarpine; D019257:Quinpirole; D007608:Kainic Acid