Prenatal cocaine exposure: long-term deficits in learning and motor performance.
We have developed a rabbit model of in utero exposure to intravenous injections of cocaine given twice daily to dams from gestational days 8-29. At the doses employed (4 mg/kg, injected twice daily), no differences were found in the body weight gain of dams, time to delivery, litter size, and body weight or other physical characteristics of the offspring. However, cocaine-exposed pups displayed an abnormal structural and neurochemical development of the anterior cingulate cortex which persisted into adulthood. In agreement with the known functions of the anterior cingulate cortex, we found that adult, sexually mature rabbits, exposed to cocaine prenatally, demonstrate impairments in motor function, alterations in associative learning and severe impairments in discrimination learning. Moreover, the alterations in discrimination learning were interpreted to be due to deficits in attentional processes. Specifically, cocaine progeny preferentially attend to more salient stimuli even when these are not relevant to the task. Consequently they have difficulty in attending to less salient but relevant stimuli when more salient but irrelevant stimuli occur in the same context. We concluded that the learning deficits are a reflection of the morphologic and neurochemical abnormalities of the anterior cingulate cortex. Alterations in dopamine function of the caudate nucleus may also contribute to the deficits in motor performance.
Romano
A G
AG
Department of Pharmacology, Allegheny University of the Health Sciences, Philadelphia, Pennsylvania 19129, USA.
Harvey
J A
JA
D000161:Acoustic Stimulation; D000818:Animals; D001288:Attention / Q000187:drug effects; D001835:Body Weight; D003042:Cocaine / Q000008:administration & dosage / Q000633:toxicity*; D004193:Discrimination Learning / Q000187:drug effects; D005260:Female; D006179:Gyrus Cinguli / Q000002:abnormalities / Q000187:drug effects* / Q000502:physiology; D007275:Injections, Intravenous; D007858:Learning / Q000187:drug effects*; D008098:Litter Size; D009043:Motor Activity / Q000187:drug effects*; D011247:Pregnancy; D011270:Pregnancy, Animal / Q000187:drug effects*; D011297:Prenatal Exposure Delayed Effects; D011817:Rabbits; D012741:Sexual Maturation
D003042:Cocaine