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Cyclic nucleotides and ethanol tolerance and dependence.

L Volicer, W K Schmidt, T P Hartz

Drug and Alcohol Dependence

|May 1, 1979

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Ethanol affects brain cyclic nucleotide and GABA levels, influencing withdrawal symptoms. Calcium and pyrazole modulate these effects, suggesting their role in alcohol withdrawal syndrome.

Area of Science:

Neuroscience
Pharmacology
Biochemistry

Background:

Ethanol consumption significantly impacts neurotransmitter systems in the brain.
Cyclic nucleotides like cyclic AMP and cyclic GMP are crucial second messengers involved in neuronal function.
GABAergic systems are known to be affected by ethanol and play a role in withdrawal.

Purpose of the Study:

To investigate the effects of acute and chronic ethanol administration on cyclic AMP, cyclic GMP, and GABA levels in different brain regions.
To explore the role of calcium and pyrazole in modulating ethanol's effects on these neurochemicals and withdrawal behaviors.
To elucidate the relationship between neurochemical changes and the expression of the ethanol withdrawal syndrome.

Main Methods:

Acute ethanol administration in animal models.

Related Experiment Videos

Intraventricular infusions of calcium and EGTA (a calcium chelator).

Measurement of cyclic AMP, cyclic GMP, and GABA levels in brain tissue.

Assessment of acoustic startle response and tolerance to ethanol's hypothermic effects during withdrawal.

Main Results:

Acute ethanol decreased cyclic AMP in some animal strains and cyclic GMP levels, which were preventable by pyrazole but not calcium.
Ethanol reduced cerebellar GABA levels specifically in stressed rats.
Calcium infusion exacerbated acoustic startle responses during withdrawal, while EGTA delayed tolerance to ethanol's hypothermic effects.

Conclusions:

The ratio of cyclic GMP to GABA levels is proposed as a key factor in the manifestation of ethanol withdrawal syndrome.
Calcium and pyrazole exhibit distinct modulatory effects on ethanol-induced neurochemical changes and withdrawal phenotypes.
These findings highlight the complex interplay of cyclic nucleotides, GABA, and calcium in alcohol's neurobiological effects and withdrawal.