Selective inhibition by adenosine of mGluR IPSPs in dopamine neurons after cocaine treatment.
With repeated exposure to psychostimulants such as cocaine and amphetamine, long-lasting changes occur in the mesolimbic dopamine system that are thought to underlie continued drug-seeking and relapse. One consequence of repeated cocaine treatment is an increase in extracellular adenosine in the ventral tegmental area (VTA), which results in tonic inhibition of synaptic input to dopamine neurons. The synapse specificity of this increased adenosine tone was examined on glutamate- and GABA-mediated responses using the selective A1 receptor antagonist 1, 3-dipropyl-8-cyclopentylxanthine (DPCPX). The slow, metabotropic glutamate receptor (mGluR)-mediated inhibitory postsynaptic potential (IPSP) was enhanced by DPCPX only in slices from psychostimulant-treated animals. Under resting conditions, DPCPX was without effect on fast excitatory postsynaptic currents (EPSCs) in slices from saline- or cocaine-treated animals. However, in the presence of amphetamine, DPCPX did augment fast EPSCs in slices from cocaine-treated rats. Although DPCPX increased GABA(B) IPSPs, the magnitude of the increase was not altered by cocaine pretreatment, even in the presence of amphetamine. This suggests that the elevated adenosine tone induced by cocaine treatment acts preferentially on glutamate terminals. Furthermore, the inhibition of the mGluR IPSP by endogenous adenosine may result in more effective burst firing mediated by glutamate afferents in cocaine-treated rats, a phenomenon known to enhance dopamine release.
Fiorillo
C D
CD
The Vollum Institute, Oregon Health Sciences University, Portland, Oregon 97201, USA.
Williams
J T
JT
D000241:Adenosine / Q000494:pharmacology*; D000661:Amphetamine / Q000494:pharmacology; D000818:Animals; D003042:Cocaine / Q000494:pharmacology*; D004298:Dopamine / Q000502:physiology*; D018765:Dopamine Uptake Inhibitors / Q000494:pharmacology*; D004594:Electrophysiology; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects*; D008297:Male; D009020:Morphine / Q000494:pharmacology; D009294:Narcotics / Q000494:pharmacology; D009474:Neurons / Q000187:drug effects*; D018408:Patch-Clamp Techniques; D051381:Rats; D017208:Rats, Wistar; D011963:Receptors, GABA-A / Q000187:drug effects; D018080:Receptors, GABA-B / Q000187:drug effects; D018094:Receptors, Metabotropic Glutamate / Q000037:antagonists & inhibitors*; D013569:Synapses / Q000187:drug effects; D014970:Xanthines / Q000494:pharmacology
D018765:Dopamine Uptake Inhibitors; D009294:Narcotics; D011963:Receptors, GABA-A; D018080:Receptors, GABA-B; D018094:Receptors, Metabotropic Glutamate; D014970:Xanthines; D009020:Morphine; C051360:1,3-dipropyl-8-cyclopentylxanthine; D000661:Amphetamine; D003042:Cocaine; D000241:Adenosine; D004298:Dopamine