Cocaine and development: a retrospective perspective

Neurobehavioral alterations evident in offspring of Sprague-Dawley rat dams exposed to 40 mg/kg/day cocaine subcutaneously from gestational days 8-20 are reviewed. Consequences for offspring are often age dependent: for instance, reliable deficits in classical conditioning are evident during the early postnatal period, whereas cognitive effects are less pervasive in adulthood, although apparent in tasks such as reversal training. Gender of offspring is another variable of importance, particularly when testing animals in adulthood, with adult male offspring being more likely than their female counterparts to exhibit alterations following the prenatal exposure regimen. Characteristics of the test situation likewise influence detection of outcome effects, with effects particularly likely to emerge under stressful testing conditions or other challenges to the organism. Under these circumstances, alterations in responsiveness to stressors also sometimes emerged in offspring of pair-fed (PF) dams (whose food intake was restricted to match that of cocaine-exposed [COC] dams); these findings perhaps should not be surprising given that pair feeding is a stressor and prenatal stress is known to alter later stressor responsiveness. Although several approaches to equate food intake or avoid pair feeding have yielded disappointing findings, one promising approach is to initiate cocaine administration prior to mating followed by exposure throughout gestation. Premating exposure to cocaine was sufficient to eliminate anorexic effects of drug delivery during pregnancy, although it remains to be seen how similar the pattern of neurobehavioral alterations that emerge with this extended exposure regimen will be to effects seen following more restricted gestational exposure.