Tags

Type your tag names separated by a space and hit enter

Ethanol blocks the reversal of prolonged dopamine inhibition of dopaminergic neurons of the ventral tegmental area.
Alcohol Clin Exp Res 2012; 36(11):1913-21AC

Abstract

BACKGROUND

Dopaminergic (DAergic) neurons of the ventral tegmental area (VTA) are important for the rewarding and reinforcing properties of alcohol and other drugs of abuse. Regulation of the firing of DAergic VTA neurons is controlled by a number of factors, including autoregulation of firing by D2 dopamine (DA) receptors. The inhibitory effects of DA on these neurons exhibit concentration- and time-dependent desensitization, which we have termed dopamine inhibition reversal (DIR), as it requires concurrent stimulation of D1/D5 and D2 receptors.

METHODS

Extracellular recording of DAergic VTA neurons in brain slices was used to test the effects of ethanol (EtOH) (10 to 80 mM) on DIR.

RESULTS

DIR was reduced by concentrations of EtOH as low as 10 mM and was blocked by higher EtOH concentrations. In addition, as we have shown that reversal of inhibition by the selective D2 agonist quinpirole can be observed in the presence of an activator of protein kinase C (PKC), we tested whether EtOH could antagonize the reversal of quinpirole inhibition in the presence of phorbol 12-myristate 13-acetate (PMA). EtOH (80 mM) blocked the reversal of quinpirole seen in the presence of PMA, suggesting that the antagonism of DIR by EtOH is owing to an action at a stage in the mechanism at or distal to PKC. Once achieved, DIR is not antagonized by EtOH.

CONCLUSIONS

The blockade by relatively low concentrations of EtOH of DIR may play an important role in the spectrum of action of EtOH on DAergic neurons of the VTA and may be important in the acute and chronic actions of EtOH on the excitability of these brain reward/reinforcement neurons.

Authors+Show Affiliations

Department of Physiology and Biophysics, University of Illinois at Chicago, IL 60612, USA.No affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural

Language

eng

PubMed ID

22551160

Citation

Nimitvilai, Sudarat, et al. "Ethanol Blocks the Reversal of Prolonged Dopamine Inhibition of Dopaminergic Neurons of the Ventral Tegmental Area." Alcoholism, Clinical and Experimental Research, vol. 36, no. 11, 2012, pp. 1913-21.
Nimitvilai S, Arora DS, McElvain MA, et al. Ethanol blocks the reversal of prolonged dopamine inhibition of dopaminergic neurons of the ventral tegmental area. Alcohol Clin Exp Res. 2012;36(11):1913-21.
Nimitvilai, S., Arora, D. S., McElvain, M. A., & Brodie, M. S. (2012). Ethanol blocks the reversal of prolonged dopamine inhibition of dopaminergic neurons of the ventral tegmental area. Alcoholism, Clinical and Experimental Research, 36(11), pp. 1913-21. doi:10.1111/j.1530-0277.2012.01814.x.
Nimitvilai S, et al. Ethanol Blocks the Reversal of Prolonged Dopamine Inhibition of Dopaminergic Neurons of the Ventral Tegmental Area. Alcohol Clin Exp Res. 2012;36(11):1913-21. PubMed PMID: 22551160.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Ethanol blocks the reversal of prolonged dopamine inhibition of dopaminergic neurons of the ventral tegmental area. AU - Nimitvilai,Sudarat, AU - Arora,Devinder S, AU - McElvain,Maureen A, AU - Brodie,Mark S, Y1 - 2012/05/02/ PY - 2012/01/05/received PY - 2012/02/20/accepted PY - 2012/5/4/entrez PY - 2012/5/4/pubmed PY - 2013/8/21/medline SP - 1913 EP - 21 JF - Alcoholism, clinical and experimental research JO - Alcohol. Clin. Exp. Res. VL - 36 IS - 11 N2 - BACKGROUND: Dopaminergic (DAergic) neurons of the ventral tegmental area (VTA) are important for the rewarding and reinforcing properties of alcohol and other drugs of abuse. Regulation of the firing of DAergic VTA neurons is controlled by a number of factors, including autoregulation of firing by D2 dopamine (DA) receptors. The inhibitory effects of DA on these neurons exhibit concentration- and time-dependent desensitization, which we have termed dopamine inhibition reversal (DIR), as it requires concurrent stimulation of D1/D5 and D2 receptors. METHODS: Extracellular recording of DAergic VTA neurons in brain slices was used to test the effects of ethanol (EtOH) (10 to 80 mM) on DIR. RESULTS: DIR was reduced by concentrations of EtOH as low as 10 mM and was blocked by higher EtOH concentrations. In addition, as we have shown that reversal of inhibition by the selective D2 agonist quinpirole can be observed in the presence of an activator of protein kinase C (PKC), we tested whether EtOH could antagonize the reversal of quinpirole inhibition in the presence of phorbol 12-myristate 13-acetate (PMA). EtOH (80 mM) blocked the reversal of quinpirole seen in the presence of PMA, suggesting that the antagonism of DIR by EtOH is owing to an action at a stage in the mechanism at or distal to PKC. Once achieved, DIR is not antagonized by EtOH. CONCLUSIONS: The blockade by relatively low concentrations of EtOH of DIR may play an important role in the spectrum of action of EtOH on DAergic neurons of the VTA and may be important in the acute and chronic actions of EtOH on the excitability of these brain reward/reinforcement neurons. SN - 1530-0277 UR - https://www.unboundmedicine.com/medline/citation/22551160/Ethanol_blocks_the_reversal_of_prolonged_dopamine_inhibition_of_dopaminergic_neurons_of_the_ventral_tegmental_area_ L2 - https://doi.org/10.1111/j.1530-0277.2012.01814.x DB - PRIME DP - Unbound Medicine ER -