Dataset Information

Chronic nicotine treatment differentially modifies acute nicotine and alcohol actions on GABA(A) and glutamate receptors in hippocampal brain slices.

ABSTRACT:

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 GABA(A) receptor currents via activation of ?7* and ?4?2* nAChRs, and increased N-methyl-D-aspartate (NMDA) and ?-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) receptor currents through ?7* receptors. While ethanol (80?mM) also increased GABA(A) 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.

SUBMITTER: Proctor WR

PROVIDER: S-EPMC3058167 | biostudies-literature | 2011 Mar

REPOSITORIES: biostudies-literature

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Publications

Chronic nicotine treatment differentially modifies acute nicotine and alcohol actions on GABA(A) and glutamate receptors in hippocampal brain slices.

Proctor William R WR Dobelis Peter P Moritz Anna T AT Wu Peter H PH

British journal of pharmacology 20110301 6

<h4>Background and purpose</h4>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.<h4>Experimental approach</h4>Acute effects of nicotine, ethanol, and both drugs on synaptic excitatory glutamatergic and inhibitory GABA ...[more]

PMID: 21133888

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Project description:BACKGROUND:Binge drinking of alcohol during adolescence is a serious public health concern with long-term consequences, including increased pain, fear, and anxiety. The periaqueductal gray (PAG) is involved in processing pain, fear, and anxiety. The effects of adolescent binge drinking on gene expression in this region have yet to be studied. METHODS:Male adolescent alcohol-preferring (P) rats were exposed to repeated binge drinking (three 1-hour sessions/d during the dark/cycle, 5 days/wk for 3 weeks starting at 28 days of age; ethanol intakes of 2.5 to 3 g/kg/session). We used RNA sequencing to assess the effects of ethanol intake on gene expression. RESULTS:Ethanol significantly altered the expression of 1,670 of the 12,123 detected genes: 877 (53%) decreased. In the glutamate system, 23 genes were found to be altered, including reduction in 7 of 10 genes for metabotropic and NMDA receptors. Subunit changes in the NMDA receptor may make it less sensitive to ethanol. Changes in GABAA genes would most likely increase the ability of the PAG to produce tonic inhibition. Five serotonin receptor genes, 6 acetylcholine receptor genes, and 4 glycine receptor genes showed decreased expression in the alcohol-drinking rats. Opioid genes (e.g., Oprk1, Oprm1) and genes for neuropeptides linked to anxiety and panic behaviors (e.g., Npy1r) had mostly decreased expression. Genes for 27 potassium, 10 sodium, and 5 calcium ion channels were found to be differentially expressed. Nine genes in the cholesterol synthesis pathway had decreased expression, including Hmgcr, encoding the rate-limiting enzyme. Genes involved in the production of myelin also had decreased expression. CONCLUSIONS:The results demonstrate that binge alcohol drinking during adolescence produces developmental changes in the expression of key genes within the PAG; many of these changes point to increased susceptibility to pain, fear, and anxiety, which could contribute to excessive drinking to relieve these negative effects.

Dataset Information

Chronic nicotine treatment differentially modifies acute nicotine and alcohol actions on GABA(A) and glutamate receptors in hippocampal brain slices.

Background and purpose

Experimental approach

Key results

Conclusions and implications

Publications

Chronic nicotine treatment differentially modifies acute nicotine and alcohol actions on GABA(A) and glutamate receptors in hippocampal brain slices.

Similar Datasets

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