Repeated cocaine exposure in vivo facilitates LTP induction in midbrain dopamine neurons. Nature 2005 Oct 13;437(7061):1027-31
Date
10/14/2005Pubmed ID
16222299Pubmed Central ID
PMC1457101DOI
10.1038/nature04050Scopus ID
2-s2.0-27144557271 (requires institutional sign-in at Scopus site) 259 CitationsAbstract
Drugs of abuse are known to cause persistent modification of neural circuits, leading to addictive behaviours. Changes in synaptic plasticity in dopamine neurons of the ventral tegmental area (VTA) may contribute to circuit modification induced by many drugs of abuse, including cocaine. Here we report that, following repeated exposure to cocaine in vivo, excitatory synapses to rat VTA dopamine neurons become highly susceptible to the induction of long-term potentiation (LTP) by correlated pre- and postsynaptic activity. This facilitated LTP induction is caused by cocaine-induced reduction of GABA(A) (gamma-aminobutyric acid) receptor-mediated inhibition of these dopamine neurons. In midbrain slices from rats treated with saline or a single dose of cocaine, LTP could not be induced in VTA dopamine neurons unless GABA-mediated inhibition was reduced by bicuculline or picrotoxin. However, LTP became readily inducible in slices from rats treated repeatedly with cocaine; this LTP induction was prevented by enhancing GABA-mediated inhibition using diazepam. Furthermore, repeated cocaine exposure reduced the amplitude of GABA-mediated synaptic currents and increased the probability of spike initiation in VTA dopamine neurons. This cocaine-induced enhancement of synaptic plasticity in the VTA may be important for the formation of drug-associated memory.
Author List
Liu QS, Pu L, Poo MMAuthor
Qing-song Liu PhD Professor in the Pharmacology and Toxicology department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
AnimalsBicuculline
Cocaine
Diazepam
Dopamine
Excitatory Postsynaptic Potentials
GABA Antagonists
GABA-A Receptor Antagonists
In Vitro Techniques
Long-Term Potentiation
Male
Memory
Mesencephalon
Neuronal Plasticity
Neurons
Picrotoxin
Rats
Rats, Sprague-Dawley
Receptors, AMPA
Receptors, GABA-A
Receptors, N-Methyl-D-Aspartate
Synapses
gamma-Aminobutyric Acid
