Prenatal cocaine exposure enhances long-term potentiation induction in rat medial prefrontal cortex.
Prenatal exposure to cocaine has been reported to produce long-lasting cognitive deficits, but the underlying mechanisms remain largely unknown. Here, we report that the induction of long-term potentiation (LTP) at excitatory synapses onto layer V pyramidal neurons in the medial prefrontal cortex (mPFC) is facilitated in rats exposed to cocaine in utero (3 mg/kg, intravenous twice daily during embryonic days 10-20). This facilitated LTP is caused by a reduction of A-type γ-aminobutyric acid (GABA(A)) receptor-mediated inhibition of mPFC pyramidal neurons. Biochemical experiments revealed a significant decrease in the surface expression of GABA(A) receptor α₁ subunits and total protein levels of γ₂ and δ subunits in mPFC slices from rats exposed to cocaine in utero. Prenatal cocaine exposure also leads to enhanced mPFC pyramidal neuronal excitability. However, the development of behavioural sensitization to repeated cocaine administration was impaired in rats that were exposed to cocaine in utero. These results suggest that prenatal cocaine exposure causes a long-lasting reduction of GABAergic inhibition in mPFC layer V pyramidal neurons, leading to an increased susceptibility of excitatory synapses to LTP induction during the postnatal period.
Department of Pharmacology, College of Medicine, National Cheng Kung University, Tainan, Taiwan.
Chiung-Chun
CC
Huang
Ying-Ching
YC
Liang
Kuei-Sen
KS
Hsu
D000818:Animals; D001640:Bicuculline / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000494:pharmacology; D003042:Cocaine / Q000008:administration & dosage / Q000494:pharmacology*; D018765:Dopamine Uptake Inhibitors / Q000008:administration & dosage / Q000494:pharmacology*; D005260:Female; D058785:GABA-A Receptor Agonists / Q000008:administration & dosage / Q000494:pharmacology; D058787:GABA-A Receptor Antagonists / Q000008:administration & dosage / Q000494:pharmacology; D017774:Long-Term Potentiation / Q000187:drug effects* / Q000502:physiology; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D009043:Motor Activity / Q000187:drug effects; D018408:Patch-Clamp Techniques; D017397:Prefrontal Cortex / Q000187:drug effects* / Q000502:physiology; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D017966:Pyramidal Cells / Q000187:drug effects* / Q000502:physiology; D011725:Pyridines / Q000008:administration & dosage / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D011963:Receptors, GABA-A / Q000378:metabolism; D000077334:Zolpidem
D018765:Dopamine Uptake Inhibitors; D058785:GABA-A Receptor Agonists; D058787:GABA-A Receptor Antagonists; D011725:Pyridines; D011963:Receptors, GABA-A; C017069:bicuculline methiodide; D000077334:Zolpidem; D003042:Cocaine; D001640:Bicuculline