title: [Effects of D1 and D2 dopamine receptor agonists and antagonists on cerebral ischemia/reperfusion injury].
abstract: Gerbil forebrain ischemia/reperfusion(I/R) injury model was used to study the effects of D(1) and D(2) receptor agonists and antagonists on neuronal apoptosis of hippocampal CA1 area. All animals were tested for habituation deficits in an open field test on the 1st, 3rd and 7th days after reperfusion. The animals were then killed, and brains underwent paraffin embedding for hematoxylin-eosin staining, in situ terminal deoxynucleotidyl transferase-mediated deoxy-UTP nick end labeling (TUNEL) staining and immunohistochemistry (bax, bcl-2). The result of open field test showed that the I/R group was significantly impaired (higher activity scores) when compared with the control group. Pretreatment with pergolide significantly reduced this habituation impairment. Forebrain ischemia for 5 min resulted in extensive CA1 apoptosis on the 3rd and 7th days after I/R injury. About 95% neurons in hippocampal CA1 area entered apoptosis and only 2%-7% pyramidal neurons stayed alive due to an inhibition of bcl-2 expression and an increase in bax expression. Pretreatment of pergolide attenuated neuronal damage caused by transient ischemia. Infusion of pergolide could induce the expression of bcl-2 and reduce the expression of bax. Pretreatment with SKF38393, SCH23390 and spiperone had no effects on these changes in this transient I/R injury model. All these results indicate that pergolide plays an important role in the protection of hippocampal neurons from apotosis through upregulating the expression of bcl-2 protein and reducing the expression of bax protein.
authors.affiliation: Center of Emergency, Affiliated Hospital of Xuzhou Medical College, Xuzhou 221002. xiaozong3@sina.com
authors.forename: Xue-Mei
authors.initials: XM
authors.lastname: Zong
authors.forename: Yin-Ming
authors.initials: YM
authors.lastname: Zeng
authors.forename: Tie
authors.initials: T
authors.lastname: Xu
authors.forename: Jian-Nong
authors.initials: JN
authors.lastname: Lü
mesh_terms: D015647:2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine / Q000494:pharmacology; D000818:Animals; D017209:Apoptosis; D001921:Brain / Q000503:physiopathology; D002545:Brain Ischemia / Q000503:physiopathology*; D018491:Dopamine Agonists / Q000494:pharmacology*; D018492:Dopamine Antagonists / Q000494:pharmacology*; D005849:Gerbillinae; D006624:Hippocampus / Q000503:physiopathology; D002546:Ischemic Attack, Transient / Q000503:physiopathology; D008297:Male; D009474:Neurons / Q000502:physiology; D018696:Neuroprotective Agents / Q000494:pharmacology*; D010479:Pergolide / Q000494:pharmacology; D016548:Prosencephalon / Q000503:physiopathology; D011518:Proto-Oncogene Proteins / Q000096:biosynthesis / Q000235:genetics; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000096:biosynthesis / Q000235:genetics; D017447:Receptors, Dopamine D1; D017448:Receptors, Dopamine D2; D015427:Reperfusion Injury / Q000503:physiopathology*; D051028:bcl-2-Associated X Protein
chemical_list: D018491:Dopamine Agonists; D018492:Dopamine Antagonists; D018696:Neuroprotective Agents; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D017447:Receptors, Dopamine D1; D017448:Receptors, Dopamine D2; D051028:bcl-2-Associated X Protein; D010479:Pergolide; D015647:2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine