Cerebral Cortex Advance Access originally published online on October 18, 2006
Cerebral Cortex 2007 17(8):1877-1888; doi:10.1093/cercor/bhl096
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Repeated Cocaine Administration Promotes Long-Term Potentiation Induction in Rat Medial Prefrontal Cortex
1 Department of Pharmacology, College of Medicine, 2 Center for Gene Regulation and Signal Transduction Research, National Cheng Kung University, Tainan 701, Taiwan
Address correspondence to Kuei-Sen Hsu, Ph.D, Department of Pharmacology, College of Medicine, National Cheng Kung University, No. 1, University Road, Tainan 701, Taiwan. Email: richard{at}mail.ncku.edu.tw
Although drug-induced adaptations in the prefrontal cortex (PFC) may contribute to several core aspects of addictive behaviors, it is not clear yet whether drugs of abuse elicit changes in synaptic plasticity at the PFC excitatory synapses. Here we report that, following repeated cocaine administration (15 mg/kg/day intraperitoneal injection for 5 consecutive days) with a 3-day withdrawal, excitatory synapses to layer V pyramidal neurons in rat medial prefrontal cortex (mPFC) become highly sensitive to the induction of long-term potentiation (LTP) by repeated correlated presynaptic and postsynaptic activity. This promoted LTP induction is caused by cocaine-induced reduction of 
-aminobutyric acid (GABA)A receptor–mediated inhibition of mPFC pyramidal neurons. In contrast, in slices from rats treated with saline or a single dose of cocaine, the same LTP induction protocol did not induce significant LTP unless the blockade of GABAA receptors. Blockade of the D1-like receptors specifically prevented the cocaine-induced enhancement of LTP. Repeated cocaine exposure reduced the GABAA receptor–mediated synaptic currents in mPFC pyramidal neurons. Biotinylation experiments revealed a significant reduction of surface GABAA receptor 
1 subunit expression in mPFC slices from repeated cocaine-treated rats. These findings support an important role for cocaine-induced enhancement of synaptic plasticity in the PFC in the development of drug-associated behavioral plasticity.
Key Words: addiction • cocaine • GABAA receptor • long-term potentiation • medial prefrontal cortex
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  H. Lu, B. Lim, and M.-m. Poo Cocaine Exposure In Utero Alters Synaptic Plasticity in the Medial Prefrontal Cortex of Postnatal Rats J. Neurosci., October 7, 2009; 29(40): 12664 - 12674. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. Pan, C. J. Hillard, and Q.-s. Liu Endocannabinoid Signaling Mediates Cocaine-Induced Inhibitory Synaptic Plasticity in Midbrain Dopamine Neurons J. Neurosci., February 6, 2008; 28(6): 1385 - 1397. [Abstract] [Full Text] [PDF]
|
|