Prenatal cocaine exposure increases mesoprefrontal dopamine neuron responsivity to mild stress.
Children whose mothers used cocaine during pregnancy appear to have an increased incidence of certain neurobehavioral deficits. Rodent models of prenatal cocaine exposure have mimicked these deficits in the offspring, yet the biochemical basis of the behavioral abnormalities is unknown. We have been able to reproduce short-term memory deficits in our rat intravenous model of prenatal cocaine exposure, and as short-term memory is dependent on the function of dopamine neurons innervating the medial prefrontal cortex, we hypothesized that prenatal cocaine induces a dysfunction in the regulation of this pathway. Here we report that mild footshock stress, which preferentially activates the mesoprefrontal dopamine system, leads to an enhanced increase in dopamine turnover in the ventromedial prefrontal cortex of adolescent (postnatal day 35-37) rats exposed to cocaine in utero, suggesting that the dopamine neurons innervating this region are hyperresponsive in these rats. Thus, this biochemical alteration may be central to some of the cognitive deficits exhibited by offspring that were exposed to cocaine during fetal development.
Elsworth
J D
JD
Department of Psychiatry, Yale University School of Medicine, New Haven, Connecticut 06520-8068, USA. john.elsworth@yale.edu
Morrow
B A
BA
Roth
R H
RH
D015102:3,4-Dihydroxyphenylacetic Acid / Q000378:metabolism; D000375:Aging / Q000187:drug effects / Q000502:physiology; D000818:Animals; D003042:Cocaine / Q000494:pharmacology*; D019970:Cocaine-Related Disorders / Q000378:metabolism / Q000503:physiopathology; D004298:Dopamine / Q000378:metabolism*; D004558:Electric Stimulation / Q000009:adverse effects; D005260:Female; D006179:Gyrus Cinguli / Q000187:drug effects / Q000196:embryology / Q000378:metabolism; D009434:Neural Pathways / Q000187:drug effects / Q000196:embryology / Q000378:metabolism; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D017397:Prefrontal Cortex / Q000187:drug effects* / Q000196:embryology / Q000378:metabolism; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D051381:Rats; D013312:Stress, Physiological / Q000378:metabolism* / Q000503:physiopathology; D017557:Ventral Tegmental Area / Q000187:drug effects* / Q000196:embryology / Q000378:metabolism
D015102:3,4-Dihydroxyphenylacetic Acid; D003042:Cocaine; D004298:Dopamine