title: Assessment of the effects of developmental toxicants: pharmacological and stress vulnerability of offspring.
abstract: From this brief summary of alterations in pharmacological and stress responsivity following gestational ethanol and cocaine exposure, a number of conclusions can be reached, although some of these conclusions are more speculative than others. Both pharmacological challenges and stress responsivity have been shown to be sensitive to the effects of prenatal ethanol as well as prenatal cocaine exposure. In terms of pharmacological sensitivity, there is some inconsistency in the findings obtained. Nevertheless, there is limited evidence to suggest that prenatal exposure to ethanol (and potentially cocaine) may increase later self-administration of the exposed drug. It should be recognized, however, that this possibility remains to be directly tested with cocaine, and needs further verification with ethanol using additional test procedures. It is interesting that a similar finding has been reported in the opiate literature: adult offspring exposed in utero to methadone exhibit an increase in subsequent morphine self-administration (Peters and Hovious 1983). Taken together, these data support the intriguing but still speculative suggestion that early chronic exposure to a drug of abuse may increase the propensity for later self-administration of that or related substances. More systematic research is needed to test this possibility and to determine whether alterations may be seen in later self-administration of other classes of abused drugs--that is, whether early drug exposure may increase the later propensity for general drug abuse. In terms of stress vulnerability, offspring exposed prenatally to ethanol predominantly have been assessed in terms of hormonal response measures, whereas the focus to date for offspring exposed prenatally to cocaine has been on alterations in behavioral responsivity to stressors. Yet prenatal exposure to either substance has been shown to result in consistent and long-lasting alterations in later responsivity to stressors in the absence of alterations in basal hormone levels in adulthood. For ethanol, these effects are particularly robust in female offspring; sex differences in stress responsivity in cocaine-exposed offspring have not been reported although few studies to date have been designed specifically to assess potential sex differences. As previously noted, the nervous system has a remarkable capacity to reorganize following insults at any age. The cost of neural reorganization following developmental insults may be associated with a decrease in adaptability that may not necessarily be evident under basal, nondrug, minimal stress, low distractibility testing conditions. Yet it is perhaps worth noting that these are the very conditions under which subjects are tested. In future work in developmental toxicity, it may prove useful to increase the demands of testing by assessing offspring under challenge conditions to reveal or unmask deficits that are not evident under basal test situations.
authors.affiliation: Center for Developmental Psychobiology, Binghamton University, State University of New York 13902-6000, USA.
authors.forename: L P
authors.initials: LP
authors.lastname: Spear
mesh_terms: D000818:Animals; D002492:Central Nervous System Depressants / Q000633:toxicity*; D003042:Cocaine / Q000633:toxicity*; D000431:Ethanol / Q000633:toxicity*; D005260:Female; D006801:Humans; D009294:Narcotics / Q000633:toxicity*; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D013315:Stress, Psychological / Q000503:physiopathology*; D013723:Teratogens / Q000633:toxicity*
chemical_list: D002492:Central Nervous System Depressants; D009294:Narcotics; D013723:Teratogens; D000431:Ethanol; D003042:Cocaine