Prenatal exposure to cocaine produces unique developmental and long-term adaptive changes in dopamine D1 receptor activity and subcellular distribution.

Stanwood GD, Levitt P
J Neurosci. 2007 27 (1): 152-7

PMID: 17202482 · PMCID: PMC6672298 · DOI:10.1523/JNEUROSCI.4591-06.2007

Low-dose intravenous cocaine administration to pregnant rabbits causes permanent structural alterations in dopamine-rich cerebral cortical areas, substantially reduced dopamine D1 receptor coupling to G(s)-protein, and deficits in cognitive function. The developmental influences of reduced D1-G(s) coupling and the underlying cellular basis are unknown. Using primary neuronal cultures derived from the medial frontal cortex and striatum of in utero saline- and cocaine-exposed embryos, spontaneous neurite outgrowth of in utero-exposed cortical neurons was greater than in control neurons. In contrast, striatal neurons exposed to cocaine in utero exhibited an entirely opposite adaptive response, with diminished spontaneous neurite outgrowth compared with saline-exposed controls. Control neurons isolated from the two structures also exhibited opposite regulatory responses to the D1 receptor agonist SKF38393 (1-phenyl-2,3,4-5-tetrahydro-(1H)-3-benzazepine-7,8-diol hydrochloride), inhibiting outgrowth in cortical cultures and stimulating outgrowth in striatal cultures. The agonist was ineffective in modulating neurite outgrowth of neurons from either structure isolated from cocaine-exposed fetuses, reflecting the reduced D1-Gs coupling. Total D1 receptor number was indistinguishable in neurons from the cocaine- and saline-exposed animals, but cell imaging and receptor binding of differentially isolated membranes showed that the lack of responsiveness was because of greatly reduced cell-surface localization of D1 receptors. These data suggest that prenatal exposure to cocaine causes a novel, long-lasting adaptive response in the subcellular distribution of D1 receptors, resulting in alterations in signaling capacity that have developmental and behavioral consequences.

MeSH Terms (15)

Adaptation, Physiological Aging Animals Brain Cocaine Female Neuronal Plasticity Neurons Pregnancy Prenatal Exposure Delayed Effects Rabbits Receptors, Dopamine D1 Subcellular Fractions Time Factors Tissue Distribution

Connections (1)

This publication is referenced by other Labnodes entities:

Links