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Published on: August 25, 2014
Prenatal cocaine exposure increases mesoprefrontal dopamine neuron responsivity to mild stress
J D Elsworth1, B A Morrow, R H Roth
1Department of Psychiatry, Yale University School of Medicine, New Haven, Connecticut 06520-8068, USA. john.elsworth@yale.edu
Insights
Prenatal cocaine exposure in rats leads to short-term memory deficits. This is linked to hyperresponsive dopamine neurons in the brain, suggesting a biochemical basis for cognitive issues in affected children.
Area of Science:
- Neuroscience
- Developmental Psychology
- Pharmacology
Background:
- Prenatal cocaine exposure is linked to neurobehavioral deficits in children.
- Rodent models replicate these deficits, but the underlying biochemistry is unclear.
- Short-term memory deficits observed in offspring are dependent on medial prefrontal cortex dopamine neuron function.
Purpose of the Study:
- To investigate the hypothesis that prenatal cocaine exposure causes dysfunction in the regulation of the mesoprefrontal dopamine pathway.
- To explore the biochemical basis of cognitive deficits in offspring exposed to cocaine in utero.
Main Methods:
- Utilized a rat intravenous model for prenatal cocaine exposure.
- Administered mild footshock stress to activate the mesoprefrontal dopamine system in adolescent rats.
- Measured dopamine turnover in the ventromedial prefrontal cortex.
Main Results:
- Rats exposed to cocaine in utero showed enhanced dopamine turnover in the ventromedial prefrontal cortex following stress.
- This suggests hyperresponsiveness of dopamine neurons innervating this region in adolescent offspring.
- Short-term memory deficits were reproduced in the rat model.
Conclusions:
- Prenatal cocaine exposure may induce a hyperresponsive mesoprefrontal dopamine system.
- This biochemical alteration could underlie cognitive deficits observed in individuals exposed to cocaine during fetal development.
- Further research is warranted to understand the long-term implications of these findings.
Abstract:
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.
