Phospholipases A2 isolated from Micrurus lemniscatus coral snake venomBehavioral, electroencephalographic, and neuropathological aspects

The present study evaluated four phospholipase A2 (PLA2) (Mlx-8, Mlx-9, Mlx-11 and Mlx-12) isolated from Micrurus lemniscatus snakevenom (Elapidae). The effects of intrahippocampal administration of these toxins have been determined on behavior, electroencephalography, andneuronal degeneration in rats. These four PLA2 toxins induced motor and EEG alterations in a dose-dependent manner. Behavioral convulsionswere characterized by clonic movements and were often accompanied by EEG alterations. Mlx toxins were convulsive but weakly epileptogenic,since low rates of seizure discharges were observed in EEG records. Neuronal injury seemed to depend on the dose of the toxin used. The highestdoses of toxins caused severe intoxication and death of some animals. The injury of hippocampal cells was characterized by massive neuronal lossand hippocampal gliosis. A high occurrence of compulsive scratching was observed. Moreover, the onset of seizures induced by Mlx toxins wasmarkedly delayed. The similarities between the effects of Mlx PLA2s and those isolated from other Elapidae snakes venoms suggest that their toxicityare probably due to their specific binding to neuronal membranes and to the catalysis of phospholipid hydrolysis, producing lysophospholipidsand fatty acids. These compounds likely disturb the membrane conformation, causing a marked increase in the release of neurotransmitters andconcurrent inhibition of vesicle fission and recycling. These toxins can be a useful tool to investigate properties of endogenous secretory PLA2sand therefore may be important both to study mechanisms involved in neurotransmitter release at nerve terminals and to explain the convulsiveproperties of PLA2s toxins.

Central nervous system supersensitivity and withdrawal from long-term treatment with barbital

The effects of withdrawal from long-term treatment with increasing concentrations of sodium barbital in the drinking water were studied in rats. Animals were tested 72 h after the removal of the drug. Withdrawal of barbital induced a significant leftward displacement of the dose-response curves obtained for the convulsive effects of strychnine, picrotoxin and 3-mercaptopropionic acid. The removal of the drug also made the rats more sensitive to convulsions elicited by sound. Baclofen and THIP were able to decrease the audiogenic response score of rats, withdrawn from barbital, in a dose-dependent way. These effects were interpreted to be a consequence of changes in the sensitivity of central GABA(A) and/or noradrenergic receptors induced by depression due to long-term administration of barbital.