OBJECTIVE To investigate the mechanism underlying dopaminergic neurotoxicity in the striatum during anoxia. METHODS Using rat striatal slices as an in vitro model, the activity of Ca2+-calmodulin-dependent protein kinase II (CCDPKII) was examined by the method of substrate phosphorylation 32P-incorporation. RESULTS Anoxia for 30 min greatly reduced CCDPKII activity by about 75 %. Reserpinization by repeated reserpine administration (1 mg . kg-1 . d-1 for 7 d, sc) preserved CCDPK II activity against the anoxia-induced decrease (about 40 % of control). The activity of CCDPKII was reduced significantly by exposure of rat striatal slices to micromolar concentrations of dopamine in the presence of extracellular Ca2+. Omission of Ca2+ in the incubation medium (with addition of 1 mmol/L egtazic acid) diminished the dopamine-induced decrease of the kinase activity. Application of apomorphine, a non-selective dopamine receptor agonist, produced a similar concentration-related decrease of CCDPKII activity. Exposure to SKF38393 (selective D1-like receptor agonist) or quinpirole (selective D2-like receptor agonist) also inhibited the kinase activity. The dopamine-induced decrease of CCDPKII activity was attenuated by preincubation with Sch-23390 (selective D1-like receptor antagonist) or domperidone (selective D2-like receptor antagonist). CONCLUSIONS Dopamine is involved in the anoxia-induced inhibition of CCDPKII activity by activation of both D1-like and D2-like receptors and influx of Ca2+, which may contribute to dopamine-mediated striatal neuronal damage.