Ethanol Disrupts the Mechanisms of Induction of Long-Term Potentiation in the Mouse Nucleus Accumbens
Article first published online: 2 MAY 2012
Copyright © 2012 by the Research Society on Alcoholism
Alcoholism: Clinical and Experimental Research
Volume 36, Issue 12, pages 2117–2125, December 2012
How to Cite
Mishra, D., Zhang, X. and Chergui, K. (2012), Ethanol Disrupts the Mechanisms of Induction of Long-Term Potentiation in the Mouse Nucleus Accumbens. Alcoholism: Clinical and Experimental Research, 36: 2117–2125. doi: 10.1111/j.1530-0277.2012.01824.x
- Issue published online: 11 DEC 2012
- Article first published online: 2 MAY 2012
- Manuscript Accepted: 6 MAR 2012
- Manuscript Received: 15 SEP 2011
- LTP ;
- Nucleus Accumbens;
- Metabotropic Glutamate Receptors;
- Dopamine Release
Long-term changes in the efficacy of glutamatergic synaptic transmission in reward-related brain regions such as the nucleus accumbens (NAc) are proposed to contribute to neuroadaptations that lead to drug addiction. Although alcohol is a widely used addictive substance, the cellular mechanisms by which it influences synaptic plasticity in the NAc are not elucidated. We therefore examined whether acute ethanol (EtOH) alters long-term potentiation (LTP) in the core region of the NAc and investigated the possible underlying mechanisms.
We measured field excitatory postsynaptic potential/population spike (fEPSP/PS) amplitude in mouse brain slices containing the NAc. We also used amperometry to detect, with carbon fiber electrode, evoked dopamine release in brain slices.
In control slices, high-frequency stimulation (HFS) induced a stable LTP. LTP was reduced in slices perfused with EtOH (50 mM). Given that induction of LTP is dependent on glutamate acting on N-methyl-d-aspartate (NMDA) receptors and group I metabotropic glutamate receptors (mGluRs), we studied the ability of EtOH to modulate these 2 classes of receptors. NMDA (20 μM) depressed the amplitude of the fEPSP/PS, but this effect was not altered by EtOH in our experimental conditions. However, EtOH reversed the ability of the group I mGluR agonist (S)-3,5-Dihydroxyphenylglycine (DHPG) (50 μM) to potentiate the depressant action of NMDA on the fEPSP/PS. We also examined whether EtOH could modulate dopamine release given that dopamine plays important roles in mediating the reinforcing actions of abused drugs and in the induction of LTP in the NAc. We found that EtOH reversibly decreased action potential-dependent dopamine release evoked by single stimulation pulses and by HFS trains in NAc slices.
These results show that EtOH impairs the induction of LTP possibly through several mechanisms that include inhibition of group I mGluR-mediated potentiation of NMDA receptor function and of evoked dopamine release. This study provides additional support for a key role of glutamatergic and dopaminergic neurotransmission in the NAc in mediating the reinforcing effects of acute alcohol.