Effects on behaviour and EEG of single chain phospholipases A2 from snake and bee venoms injected into rat brain: search for a functional antagonism.

Abstract

Three phospholipase A2 (PLA2s), OS1 and OS1 purified from the taipan snake venom Oxyuranus scutellatus scutellatus and bee venom PLA2 were injected to rats by the intracerebroventricular route. OS1 showed no sign of neurotoxicity at doses at which OS2 and bee venom PLA2 produced multiform dose-dependent behavioural effects including motor disturbances (stereotyped movements), compulsive scratching, convulsions and breathing difficulties. EEG recordings showed at the very time when the animal was motionless the induction of several episodes of a low frequency hippocampal theta rhythm, index of long-term changes in synaptic neuroplasticity. Spike-wave discharges were also produced but the occurrence was not systematic. These seizures were often accompanied with behavioural convulsions. Blockers of NMDA receptors and drugs modifying the GABAergic transmission could not abolish the neurotoxic effects of PLA2s except for diazepam (10 mg/kg intraperitoneally) that prevented only OS2-induced disturbances. Blockers of L-type Ca2+ channels and K+ channel openers were also without effect. The toxicity of OS2 and bee venom PLA2 is probably due to their initial specific binding to their neuronal receptor sites.