Cocaine exposure in utero alters synaptic plasticity in the medial prefrontal cortex of postnatal rats.
Cocaine exposure during pregnancy causes abnormality in fetal brain development, leading to cognitive dysfunction of the offspring, but the underlying cellular mechanism remains mostly unclear. In this study, we examined synaptic functions in the medial prefrontal cortex (mPFC) of postnatal rats that were exposed to cocaine in utero, using whole-cell recording from mPFC layer V pyramidal neurons in acute brain slices. Cocaine exposure in utero resulted in a facilitated activity-induced long-term potentiation (LTP) of excitatory synapses on these pyramidal neurons and an elevated neuronal excitability in postnatal rat pups after postnatal day 15 (P15). This facilitated LTP could be primarily attributed to the reduction of GABAergic inhibition. Biochemical assays of isolated mPFC tissue from postnatal rats further showed that cocaine exposure in utero caused a marked reduction in the surface expression of GABA(A) receptor subunits alpha1, beta2, and beta3, but had no effect on glutamate receptor subunit GluR1. Both facilitated LTP and reduced surface expression of GABA(A) receptors persisted in rats up to at least P42. Finally, the behavioral consequence of cocaine exposure in utero was reflected by the reduction in the sensitivity of locomotor activity in postnatal rats to cocaine and the dopamine receptor agonist apomorphine. Since the mPFC is an important part of the reward circuit in the rat brain and plays important roles in cognitive functions, these findings offer new insights into the cellular mechanism underlying the adverse effects of cocaine exposure in utero on brain development and cognitive functions.
Lu
Hui
H
Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, CA 94720, USA.
Lim
Byungkook
B
Poo
Mu-ming
MM
D000818:Animals; D001058:Apomorphine / Q000008:administration & dosage; D003042:Cocaine / Q000633:toxicity*; D005260:Female; D008124:Locomotion / Q000187:drug effects; D017774:Long-Term Potentiation / Q000187:drug effects; D009043:Motor Activity / Q000187:drug effects; D009473:Neuronal Plasticity / Q000187:drug effects*; D018408:Patch-Clamp Techniques; D017397:Prefrontal Cortex / Q000196:embryology*; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D017966:Pyramidal Cells / Q000187:drug effects / Q000196:embryology; D051381:Rats; D017207:Rats, Sprague-Dawley; D011963:Receptors, GABA-A / Q000378:metabolism; D009435:Synaptic Transmission / Q000187:drug effects
D011963:Receptors, GABA-A; D003042:Cocaine; D001058:Apomorphine