Selective Inhibition By Adenosine of mGluR IPSPs in Dopamine Neurons Following Cocaine Treatment. Christopher D. Fiorillo and John T. Williams. The Vollum Institute, L474, Oregon Health Sciences University, 3181 SW Sam Jackson Park Rd, Portland, OR 97201.
APStracts 6:0552N, 1999.
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 (Bonci and Williams 1996). The synapse specificity of this increased adenosine tone was examined on glutamate- and GABA-mediated responses using the selective A1 receptor antagonist DPCPX. The slow, metabotropic glutamate receptor (mGluR)-mediated IPSP was enhanced by DPCPX only in slices from psychostimulant-treated animals. Under resting conditions, DPCPX was without effect on fast 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 GABAB 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.
Received 27 August 1999; accepted in final form 29 October 1999.
APS Manuscript Number J734-9.
Article publication pending Journal of Neurophysiology.
ISSN 1080-4757 Copyright 1999 The American Physiological Society.
Published in APStracts on 21 December 1999