Modifications of the input currents on VTA dopamine neurons following acute versus chronic cocaine exposure

Avner Michaeli, Henry Matzner, Tatyana Poltyrev, Rami Yaka*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

5 Scopus citations

Abstract

Excitatory synapses on dopamine (DA) neurons in the ventral tegmental area (VTA) are modulated following exposure to various addictive drugs, including cocaine. Previously we have shown that cocaine affects GABA A receptor (GABA AR)-mediated neurotransmission in VTA DA neurons. This finding led us to reexamine the modulation of the excitatory synapse on these neurons in response to cocaine exposure, while the activity of GABA AR is uninterrupted. Using rat brain slices, evoked post synaptic currents (ePSC) were monitored and inhibitors of NMDA receptor (NMDAR) and AMPA receptor (AMPAR) were gradually added to inhibitors-free bath solution. Modifications in the efficacy of the excitatory synapses were evaluated by comparing AMPAR-mediated and NMDAR-mediated currents (AMPA/NMDA ratio). The lack of GABA AR inhibitors enabled us to examine parallel changes in the relation between GABA AR-mediated and NMDAR-mediated currents (GABA A/NMDA ratio). First, we found that AMPA/NMDA ratio measured under complete availability of GABA AR, is significantly higher than the ratio measured under GABA AR blockade. In addition, GABA A/NMDA ratio, but not AMPA/NMDA ratio, is augmented a few hours following in vitro acute cocaine exposure. When measured 24 h after in vivo single cocaine injection, no change in GABA A/NMDA ratio was observed, however, the AMPA/NMDA ratio was found to be significantly higher. Finally, a decrease in both ratios was detected in rats repeatedly injected with cocaine. Taken together, these results lead to a better understanding of the means by which cocaine modifies synaptic inputs on VTA DA neurons. The parallel changes in GABA A/NMDA ratio may suggest an interaction between inhibitory and excitatory neural systems.

Original languageAmerican English
Pages (from-to)1834-1840
Number of pages7
JournalNeuropharmacology
Volume62
Issue number4
DOIs
StatePublished - Mar 2012

Bibliographical note

Funding Information:
This research was supported by the Israel Science Foundation (grant No. 144/10 ) and the National Institute for Psychobiology in Israel founded by the Charles E. Smith family. R. Yaka is affiliated with the David R. Bloom Center for Pharmacy and the Brettler Center for Research in Molecular Pharmacology and Therapeutics, School of Pharmacy, The Hebrew University of Jerusalem.

Keywords

  • AMPA receptor
  • GABA receptor
  • NMDA receptor
  • Picrotoxin
  • Ratio
  • ePSC

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