Department of Pharmacology, Allegheny University of the Health Sciences, Philadelphia, Pennsylvania 19129, USA
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.
