DOPAMINE D-2 RECEPTOR AGONISTS PROTECT AGAINST ISCHEMIA-INDUCED HIPPOCAMPAL NEURODEGENERATION IN GLOBAL CEREBRAL-ISCHEMIA

To characterise the role played by dopamine receptors in ischaemic bra in damage, we have evaluated the effects of pergolide, bromocriptine a nd lisuride (dopamine D-2 receptor agonists), haloperidol(a dopamine D -2 receptor antagonist), tetrahydro-7,8,dihydroxy-1-phenyl-1H-3-benzaz epine (SKF 38393; a dopamine D-1 receptor agonist) and (R)-(+)-8-chlor o 2,3,4,5-tetra-hydro-3-methyl-5-phenyl-1 H-3-benzazepin-7-ol (SCH 233 90; a dopamine D-1 receptor antagonist) in the gerbil model of global cerebral ischaemia. Ischaemia was induced by 5 min of bilateral caroti d artery occlusion under halothane anaesthesia. Sham operated animals were used as controls. Pergolide (0.5 or 1.0 mg/kg i.p), bromocriptine (0.5 or 1.0 mg/kg i.p.), lisuride (0.5 or 1.0 mg/kg i.p.), SCH 23390 (0.1 or 1.0 mg/kg i.p.), haloperidol (0.5, 1.0 or 2 mg/kg i.p.) and SK F 38393 (1.0 or 2 mg/kg i.p.) were administered 1 h before occlusion. Five-minute-occluded animals had extensive damage in the CAI region of the hippocampus 5 days after surgery. Pergolide 0.5 and 1.0 mg/kg i.p . provided significant (P < 0.05 and P < 0.01, respectively) neuroprot ection against the ischaemia-induced hippocampal damage. Bromocriptine and lisuride also provided significant (P < 0.05) neuroprotection, bu t only at the higher 1.0 mg/kg dose. In contrast, the dopamine D-2 rec eptor antagonist (haloperidol), the dopamine D-1 receptor agonist (SKF 38393) and the dopamine D-1 receptor antagonist (SCH 23390) failed to provide any neuroprotection in the model. These results support studi es indicating that dopamine is important in ischaemic situations. The results also indicate that dopamine D-2 receptor agonists are neuropro tective against ischaemia-induced brain injury and may play a role in neurodegenerative disorders. (C) 1998 Elsevier Science B.V. All rights reserved.