Chronic nicotine treatment differentially modifies acute nicotine and alcohol actions on GABAA and glutamate receptors in hippocampal brain slices
Article first published online: 22 FEB 2011
British Journal of Pharmacology © 2011 The British Pharmacological Society. No claim to original US government works
British Journal of Pharmacology
Volume 162, Issue 6, pages 1351–1363, March 2011
How to Cite
Proctor, W. R., Dobelis, P., Moritz, A. T. and Wu, P. H. (2011), Chronic nicotine treatment differentially modifies acute nicotine and alcohol actions on GABAA and glutamate receptors in hippocampal brain slices. British Journal of Pharmacology, 162: 1351–1363. doi: 10.1111/j.1476-5381.2010.01141.x
- Issue published online: 22 FEB 2011
- Article first published online: 22 FEB 2011
- Accepted manuscript online: 6 DEC 2010 06:14AM EST
- Received; 23 April 2010; Revised; 2 November 2010; Accepted; 4 November 2010
- GABAA receptor;
- NMDA receptor;
- AMPA receptor;
- nicotinic receptor
BACKGROUND AND PURPOSE Tobacco and alcohol are often co-abused producing interactive effects in the brain. Although nicotine enhances memory while ethanol impairs it, variable cognitive changes have been reported from concomitant use. This study was designed to determine how nicotine and alcohol interact at synaptic sites to modulate neuronal processes.
EXPERIMENTAL APPROACH Acute effects of nicotine, ethanol, and both drugs on synaptic excitatory glutamatergic and inhibitory GABAergic transmission were measured using whole-cell recording in hippocampal CA1 pyramidal neurons from brain slices of mice on control or nicotine-containing diets.
KEY RESULTS Acute nicotine (50 nM) enhanced both GABAergic and glutamatergic synaptic transmission; potentiated GABAA receptor currents via activation of α7* and α4β2* nAChRs, and increased N-methyl-d-aspartate (NMDA) and α-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) receptor currents through α7* receptors. While ethanol (80 mM) also increased GABAA currents, it inhibited NMDA currents. Although ethanol had no effect on AMPA currents, it blocked nicotine-induced increases in NMDA and AMPA currents. Following chronic nicotine treatment, acute nicotine or ethanol did not affect NMDA currents, while the effects of GABAergic responses were not altered.
CONCLUSIONS AND IMPLICATIONS Acute ethanol ingestion selectively attenuated nicotine enhancement of excitatory glutamatergic NMDA and AMPA receptor function, suggesting an overall reduction in excitatory output from the hippocampus. It also indicated that ethanol could decrease the beneficial effects of nicotine on memory performance. In addition, chronic nicotine treatment produced tolerance to the effects of nicotine and cross-tolerance to the effects of ethanol on glutamatergic activity, leading to a potential increase in the use of these drugs.