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

Avner Michaeli; Henry Matzner; Tatyana Poltyrev; Rami Yaka

doi:10.1016/j.neuropharm.2011.12.005

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

School of Pharmacy

Research output: Contribution to journal › Article › peer-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 language	English
Pages (from-to)	1834-1840
Number of pages	7
Journal	Neuropharmacology
Volume	62
Issue number	4
DOIs	https://doi.org/10.1016/j.neuropharm.2011.12.005
State	Published - 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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This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1016/j.neuropharm.2011.12.005

Cite this

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title = "Modifications of the input currents on VTA dopamine neurons following acute versus chronic cocaine exposure",

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.",

keywords = "AMPA receptor, GABA receptor, NMDA receptor, Picrotoxin, Ratio, ePSC",

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N2 - 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.

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

Abstract

Bibliographical note

Keywords

UN SDGs

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