Perinatal lead exposure modifies the locomotor effects of ethanol in caenorhabditis elegans: role of ethanol metabolism

ALBRECHT, PAULA A.; CARRANZA, ANDREA; DEZA PONZIO, R; LUCIA E. FERNANDEZ-HUBEID; CANCELA L.M; ASSIS R.; ASCHNER M.; VIRGOLINI M

San Diego, California

Congreso; Society for Neuroscience; 2018

SfN

Previous studies have demonstrated that developmental lead (Pb) exposure induces higher susceptibilityto several responses to ethanol in rats. Caenorhabditis elegans has been used to study theneurobehavioral responses to drugs, including ethanol. Within this context, an acute ethanol exposureinduces 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 theL1 stage. Thereafter, they were washed and transferred to a new plate free of Pb with food for 48 h. Theethanol effects on motility were evaluated in L3 controls and perinatally Pb-exposed worms, 2 h after theethanol concentration in the agar reached 100, 200 or 400 mM. The average speed of ten worms wasregistered for 2 min period either 10 min or 30 min after the onset of ethanol exposure to evaluate theinitial depressor response that was followed by a recuperation effect characteristic of ethanol effects onmotility. The results demonstrate that 200 mM of ethanol was the optimal dose to elicit differencesbetween the control and Pb-exposed groups. In effect, the sedative effects of the drug were observed inthe controls opposite to the hyperactivity manifested in the Pb-exposed animals. In addition, the use of amutant strain that lacks the alcohol dehydrogenase (ADH)-like enzyme which metabolizes ethanol toacetaldehyde prevented the manifestation of these differences. Thus, the enduring hypermotility observedin the Pb group after ethanol exposure suggests a potentiation in the development of tolerance to thesedative effects of ethanol. Furthermore, the acetaldehyde seems to play a critical role in ethanolmetabolism in the manifestation of these effects in the Pb-exposed worms