EFFECTS OF ALPHA(2)-ADRENOCEPTOR ANTAGONISTS AND IMIDAZOLINE(2)-RECEPTOR LIGANDS ON NEURONAL DAMAGE IN GLOBAL-ISCHEMIA IN THE RAT

1, In the present study the neuroprotective effects of 3 mg/kg idazoxa n, an alpha(2)-adrenoceptor antagonist and imidazoline(2)-receptor (I- 2-receptor) ligand, 3 mg/kg methoxyidazoxan, a specific alpha(2)-adren oceptor antagonist, and 0.6 and 3 mg/kg BU224, a selective I-2-recepto r ligand, were evaluated following 10 min of global ischaemia in rats, 2, Neuronal cell counts in the CA1 region of the hippocampus 8 days p ostischaemia indicated 46-96% cell loss compared with control(P<0.001) and a 320% increase in [H-3]-PK11195 binding (P<0.001) used as a mark er of gliosis, No significant neuroprotective effect could be detected on these markers of neuronal damage in the active treatment groups. I n a subset of idazoxan-treated rats, neuronal loss and gliosis was min imal. 3. Mean body temperature over 3 h postischaemia was lower in ida zoxan-treated rats than in the other treatment groups (P<0.001) and th ere was a correlation between mean body temperature and cell counts (P <0.01) and mean body temperature and gliosis in this group (P = 0.057) , 4, These results indicate that at the doses used neither BU224 nor m ethoxyidazoxan are neuroprotective in this ischaemia model and they ra ise the possibility that any neuroprotective effect of idazoxan may be related to hypothermic effects of the drug.