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Are changes in neuronal calcium channels involved in ethanol tolerance?
1Division of Anaesthesia, Clinical Research Centre, Harrow, Middlesex, Great Britain.
The Journal of Pharmacology and Experimental Therapeutics
|September 1, 1989
Summary
Concurrent administration of nitrendipine, a dihydropyridine calcium channel antagonist, prevented ethanol tolerance development in rats. This suggests calcium channels are involved in adaptations to chronic ethanol exposure.
Area of Science:
- Neuroscience
- Pharmacology
Background:
- Chronic ethanol consumption leads to tolerance, a reduced response to the drug's effects.
- Dihydropyridine binding sites in the brain are altered by chronic ethanol exposure.
Purpose of the Study:
- To investigate the role of dihydropyridine calcium channels in the development of ethanol tolerance.
- To determine if nitrendipine can prevent ethanol tolerance.
Main Methods:
- Ethanol tolerance was induced in rats via repeated intraperitoneal injections.
- Performance on the rotarod apparatus was used to measure ethanol-induced ataxia.
- Dihydropyridine binding sites in rat cerebral cortex were quantified.
Main Results:
- Concurrent nitrendipine administration prevented the development of tolerance to ethanol's ataxic effects.
- Nitrendipine also prevented the increase in dihydropyridine binding sites caused by chronic ethanol.
- The effects of nitrendipine were not attributable to changes in body temperature, blood pressure, or ethanol concentration.
Conclusions:
- Dihydropyridine-sensitive calcium channels appear to play a role in the neuroadaptive changes associated with chronic ethanol use.
- Targeting these calcium channels may offer a strategy to mitigate ethanol tolerance.