Repeated cocaine administration promotes long-term potentiation induction in rat medial prefrontal cortex.
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 gamma-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 GABA(A) receptors. Blockade of the D1-like receptors specifically prevented the cocaine-induced enhancement of LTP. Repeated cocaine exposure reduced the GABA(A) receptor-mediated synaptic currents in mPFC pyramidal neurons. Biotinylation experiments revealed a significant reduction of surface GABA(A) receptor alpha1 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.
Huang
Chiung-Chun
CC
Department of Pharmacology, College of Medicine, National Cheng Kung University, Tainan, Taiwan.
Lin
Hsiao-Ju
HJ
Hsu
Kuei-Sen
KS
D000818:Animals; D001552:Benzazepines / Q000494:pharmacology; D002227:Carbazoles / Q000494:pharmacology; D003042:Cocaine / Q000008:administration & dosage / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D018492:Dopamine Antagonists / Q000494:pharmacology; D018765:Dopamine Uptake Inhibitors / Q000008:administration & dosage / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D004594:Electrophysiology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D007211:Indoles / Q000494:pharmacology; D017774:Long-Term Potentiation / Q000187:drug effects*; D008297:Male; D009043:Motor Activity / Q000187:drug effects; D018408:Patch-Clamp Techniques; D017397:Prefrontal Cortex / Q000187:drug effects*; D017966:Pyramidal Cells / Q000187:drug effects; D011758:Pyrroles / Q000494:pharmacology; D020891:Raclopride / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D011956:Receptors, Cell Surface / Q000187:drug effects; D017447:Receptors, Dopamine D1 / Q000187:drug effects; D011963:Receptors, GABA-A / Q000187:drug effects; D013268:Stimulation, Chemical; D005680:gamma-Aminobutyric Acid / Q000502:physiology
D001552:Benzazepines; D002227:Carbazoles; D018492:Dopamine Antagonists; D018765:Dopamine Uptake Inhibitors; D004791:Enzyme Inhibitors; C546242:Gabra1 protein, rat; D007211:Indoles; D011758:Pyrroles; D011956:Receptors, Cell Surface; D017447:Receptors, Dopamine D1; D011963:Receptors, GABA-A; D020891:Raclopride; D005680:gamma-Aminobutyric Acid; C057416:KT 5720; D003042:Cocaine