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Modifications of the input currents on VTA dopamine neurons following acute versus chronic cocaine exposure.
Neuropharmacology. 2012 Mar; 62(4):1834-40.N

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(A)R)-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(A)R 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(A)R inhibitors enabled us to examine parallel changes in the relation between GABA(A)R-mediated and NMDAR-mediated currents (GABA(A)/NMDA ratio). First, we found that AMPA/NMDA ratio measured under complete availability of GABA(A)R, is significantly higher than the ratio measured under GABA(A)R 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.

Authors+Show Affiliations

Institute for Drug Research, School of Pharmacy, Faculty of Medicine, The Hebrew University of Jerusalem, Jerusalem, Israel.No affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

22197515

Citation

Michaeli, Avner, et al. "Modifications of the Input Currents On VTA Dopamine Neurons Following Acute Versus Chronic Cocaine Exposure." Neuropharmacology, vol. 62, no. 4, 2012, pp. 1834-40.
Michaeli A, Matzner H, Poltyrev T, et al. Modifications of the input currents on VTA dopamine neurons following acute versus chronic cocaine exposure. Neuropharmacology. 2012;62(4):1834-40.
Michaeli, A., Matzner, H., Poltyrev, T., & Yaka, R. (2012). Modifications of the input currents on VTA dopamine neurons following acute versus chronic cocaine exposure. Neuropharmacology, 62(4), 1834-40. https://doi.org/10.1016/j.neuropharm.2011.12.005
Michaeli A, et al. Modifications of the Input Currents On VTA Dopamine Neurons Following Acute Versus Chronic Cocaine Exposure. Neuropharmacology. 2012;62(4):1834-40. PubMed PMID: 22197515.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Modifications of the input currents on VTA dopamine neurons following acute versus chronic cocaine exposure. AU - Michaeli,Avner, AU - Matzner,Henry, AU - Poltyrev,Tatyana, AU - Yaka,Rami, Y1 - 2011/12/14/ PY - 2011/07/21/received PY - 2011/11/30/revised PY - 2011/12/07/accepted PY - 2011/12/27/entrez PY - 2011/12/27/pubmed PY - 2012/7/28/medline SP - 1834 EP - 40 JF - Neuropharmacology JO - Neuropharmacology VL - 62 IS - 4 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(A)R)-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(A)R 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(A)R inhibitors enabled us to examine parallel changes in the relation between GABA(A)R-mediated and NMDAR-mediated currents (GABA(A)/NMDA ratio). First, we found that AMPA/NMDA ratio measured under complete availability of GABA(A)R, is significantly higher than the ratio measured under GABA(A)R 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. SN - 1873-7064 UR - https://www.unboundmedicine.com/medline/citation/22197515/Modifications_of_the_input_currents_on_VTA_dopamine_neurons_following_acute_versus_chronic_cocaine_exposure_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0028-3908(11)00509-0 DB - PRIME DP - Unbound Medicine ER -