CONICET | Buscador de Institutos y Recursos Humanos

Previous studies have demonstrated that developmental lead (Pb) exposure induces higher susceptibility to several responses to ethanol in rats. Caenorhabditis elegans has been used to study the neurobehavioral responses to drugs, including ethanol. Within this context, an acute ethanol exposure induces an initial sensitization and afterward tolerance to its sedative effects on motility. Wild-type (N2) nematodes in the L3 stage were exposed to Pb(NO3)2 5mg/L during 96 h until their progeny reached the L1 stage. Thereafter, they were washed and transferred to a new plate free of Pb with food for 48 h. The ethanol effects on motility were evaluated in L3 controls and perinatally Pb-exposed worms, 2 h after the ethanol concentration in the agar reached 100, 200 or 400 mM. The average speed of ten worms was registered for 2 min period either 10 min or 30 min after the onset of ethanol exposure to evaluate the initial depressor response that was followed by a recuperation effect characteristic of ethanol effects on motility. The results demonstrate that 200 mM of ethanol was the optimal dose to elicit differences between the control and Pb-exposed groups. In effect, the sedative effects of the drug were observed in the controls opposite to the hyperactivity manifested in the Pb-exposed animals. In addition, the use of a mutant strain that lacks the alcohol dehydrogenase (ADH)-like enzyme which metabolizes ethanol to acetaldehyde prevented the manifestation of these differences. Thus, the enduring hypermotility observed in the Pb group after ethanol exposure suggests a potentiation in the development of tolerance to the sedative effects of ethanol. Furthermore, the acetaldehyde seems to play a critical role in ethanol metabolism in the manifestation of these effects in the Pb-exposed worms. Supported by MinCyT, CONICET and SeCyT-UNC, Argentina.