Neurobehavioral changes produced by developmental exposure to environmental pollutants

The central nervous system (CNS) of rats reaches functional maturation several weeks after birth. Contrast this to other organs, in which the basic structure and function are completed in utero or shortly after birth. Therefore, the CNS is susceptible to insult for a longer portion of development than other organs. Moreover, the timing of exposure, whether discrete or long term, seems to play a crucial role in determining structural and/or functional alterations.A large body of evidence suggests that behaviour is a sensitive indicator of subtle damages in CNS function caused by exposure to chemicals at dose levels below those associated with overt neurologic signs and that developmental exposure to psychotropic drugs (e.g., neuroleptics, benzodiazepines) and environmental toxicants (e.g., methylmercury, lead) produces neurobehavioral changes which differ markedly from those occurring in response to their administration to mature animals.In this regard, our group has been involved in research programs dealing with the characterization of neurobehavioral effects produced by developmental exposure to environmental pollutants (Di Giovanni et al., 1993, Di Giovanni et al., 1994). In particular, the interest has been recently focused on the assessment of outcomes that follows the developmental exposure to carbon monoxide (CO), a product of incomplete combustion found in elevated concentrations in many urban areas and one of the constituents of cigarette smoke.Several findings have shown that gestational exposure to relatively mild concentrations of CO induces neurobehavioral abnormalities in rats, including lower activity levels through the preweaning, delayed development of homing behavior and negative geotaxis as well as altered ontogeny of emotional reactivity (see for references Annau and Fechter, 1994). However, only few studies have been addressed to the evaluation of long term neurobehavioral changes elicited by prenatal exposure to low concentrations of this gas.Since previous findings have shown alterations in the acquisition of active avoidance schedule (Mactutus and Fechter, 1984; Di Giovanni et al., 1993) and impaired sexual behavior (unpublished data) in young adult rats prenatally exposed to relatively mild concentrations of CO (0, 75 and 150 ppm from day 0 to day 20 of pregnancy), the aim of our recent studies was to evaluate whether these behavioral alterations would dissipate at a later age.The results show that CO (150 ppm)-exposed male rats (18-month old) subjected to an active avoidance task still exhibited notable learning deficit. Moreover, prenatal exposure to this toxicant significantly impaired reacquisition of this schedule in 18-month old animals previously trained at 3-months of age. The impairment in both acquisition and reacquisition of an active avoidance task did not appear to be due to alterations of a nonassociative nature. In fact, changes in emotional reactivity seem to be absent as shown by the analysis of unconditioned responses latencies which were not influenced by CO exposure. Moreover, spontaneous crossings during intertrial intervals were not significantly affected in rats exposed to this gas during gestation (De Salvia et al., 1995).Further studies have also shown that some alterations in sexual performance of CO-exposed male animals were long lasting. In fact, a significant increase in mount intromission latency in 365-day old rats exposed to CO (150 ppm) during pregnancy was found. Furthermore, the significant increase in mount-intromission frequency exhibited by young adult CO-exposed rats lasted up to 200 days of age in both 75 and 150 ppm CO-treated groups.The results described in this paper, as well as results obtained by other investigators, confirm the deleterious and irreversible effects of prenatal carbon monoxide exposure in animals. These data show that behavioral, neurochemical, neuropathological and neurophysiological alterations can be documented following moderate carboxyhemoglobin levels during fetal development, and that the fetal brain is extremely sensitive to the toxic effects of carbon monoxide. To date, very few human studies have been done to verify these findings in children of mothers who smoke cigarettes during pregnancy. Because cigarette smoke is the major source of carbon monoxide exposure in the human population, and epidemiological studies have shown that it increases neonatal mortality, it would seem prudent to scrutinize the potential neurotoxic effects of offspring whose mothers smoke.