Abstract
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 (GABAA) receptor-mediated inhibition of mPFC pyramidal neurons. Biochemical experiments revealed a significant decrease in the surface expression of GABAA 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.
| Original language | English |
|---|---|
| Pages (from-to) | 431-443 |
| Number of pages | 13 |
| Journal | International Journal of Neuropsychopharmacology |
| Volume | 14 |
| Issue number | 4 |
| DOIs | |
| Publication status | Published - 2011 Jan 1 |
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All Science Journal Classification (ASJC) codes
- Pharmacology
- Psychiatry and Mental health
- Pharmacology (medical)
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Prenatal cocaine exposure enhances long-term potentiation induction in rat medial prefrontal cortex. / Huang, Chiung Chun; Liang, Ying Ching; Hsu, Kuei-Sen.
In: International Journal of Neuropsychopharmacology, Vol. 14, No. 4, 01.01.2011, p. 431-443.Research output: Contribution to journal › Article
TY - JOUR
T1 - Prenatal cocaine exposure enhances long-term potentiation induction in rat medial prefrontal cortex
AU - Huang, Chiung Chun
AU - Liang, Ying Ching
AU - Hsu, Kuei-Sen
PY - 2011/1/1
Y1 - 2011/1/1
N2 - 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 (GABAA) receptor-mediated inhibition of mPFC pyramidal neurons. Biochemical experiments revealed a significant decrease in the surface expression of GABAA 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.
AB - 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 (GABAA) receptor-mediated inhibition of mPFC pyramidal neurons. Biochemical experiments revealed a significant decrease in the surface expression of GABAA 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.
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UR - http://www.scopus.com/inward/citedby.url?scp=85027956423&partnerID=8YFLogxK
U2 - 10.1017/S1461145710000258
DO - 10.1017/S1461145710000258
M3 - Article
VL - 14
SP - 431
EP - 443
JO - International Journal of Neuropsychopharmacology
JF - International Journal of Neuropsychopharmacology
SN - 1461-1457
IS - 4
ER -