Effect of piribedil, a D-2 dopaminergic agonist, on dopamine, amino acids, and free radicals in gerbil brain after cerebral ischemia.
The excitatory amino acids (EAA) are involved in the pathogenesis of the cerebral ischemia. Moreover, several investigators have demonstrated that a considerable amount of dopamine (DA) is released in the striatum after ischemia reperfusion/insult (IRI). Recently, studies have demonstrated in vitro, that D-2 agonist, at the level of striatum and retina, may represent a powerful signal to inhibit release of excitatory amino acids implicated in cerebral ischemia. Therefore we have been incited to test, in vivo, the action of a D-2 agonist, piribedil, on gerbil brain after IRI. We have used the Stroke Index (SI); then to precise the mechanism of action, we have determined the levels of dopamine, EAA, and hydroxyl-free radicals (OH), in striatum, hippocampus, and hemisphere. Piribedil, administered at dose of 10 mg/kg, per os, 60 min before induction of transient cerebral ischemia in gerbils, presents a neuroprotective effect, as measured by SI and significantly reverses the increase of DA, EAA, and OH induced by IRI. The mechanism of action of piribedil could be related to its D-2 agonist property.
Delbarre
B
B
Faculté de Médecine, Tours, France.
Delbarre
G
G
Rochat
C
C
Calinon
F
F
D000818:Animals; D001921:Brain / Q000098:blood supply / Q000187:drug effects* / Q000378:metabolism; D002561:Cerebrovascular Disorders / Q000517:prevention & control; D003342:Corpus Striatum / Q000187:drug effects; D004298:Dopamine / Q000378:metabolism; D018846:Excitatory Amino Acids / Q000378:metabolism; D005849:Gerbillinae; D006624:Hippocampus / Q000187:drug effects; D018696:Neuroprotective Agents / Q000494:pharmacology*; D010891:Piribedil / Q000494:pharmacology*; D017448:Receptors, Dopamine D2 / Q000819:agonists*; D015427:Reperfusion Injury / Q000517:prevention & control*
D018846:Excitatory Amino Acids; D018696:Neuroprotective Agents; D017448:Receptors, Dopamine D2; D010891:Piribedil; D004298:Dopamine