Selective inhibition by adenosine of mGluR IPSPs in dopamine neurons aftercocaine treatment

With repeated exposure to psychostimulants such as cocaine and amphetamine, long lasting changes occur in the mesolimbic dopamine system that are thou ght to underlie continued drug-seeking and relapse. One consequence of repe ated cocaine treatment is an increase in extracellular adenosine in the ven tral tegmental area (VTA), which results in tonic inhibition of synaptic in put to dopamine neurons. The synapse specificity of this increased adenosin e tone was examined on glutamate- and GABA-mediated responses using the sel ective Al receptor antagonist 1,3-dipropyl-8-cyclopentylxanthine (DPCPX). T he slow, metabotropic glutamate receptor (mGluR)-mediated. inhibitory posts ynaptic potential (IPSP) was enhanced by DPCPX only in slices from psychost imulant-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 di d augment fast EPSCs in slices from cocaine-treated rats. Although DPCPX in creased GABA, IPSPs, the magnitude of the increase was not altered by cocai ne pretreatment, even in the presence of amphetamine. This suggests that th e elevated adenosine tone induced by cocaine treatment acts preferentially on glutamate terminals. Furthermore, the inhibition of the mGluR IPSP by en dogenous adenosine may result in more effective burst firing mediated by gl utamate afferents in cocaine-treated rats, a phenomenon known to enhance do pamine release.