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Murine Drinking Models in the Development of Pharmacotherapies for Alcoholism: Drinking in the Dark and Two-bottle Choice
Published on: January 7, 2019
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Dopamine synthesis in alcohol drinking-prone and -resistant mouse strains
Cody A Siciliano1, Jason L Locke1, Tiffany A Mathews2
1Department of Physiology and Pharmacology, Wake Forest School of Medicine, Winston-Salem, NC, USA.
Alcohol (Fayetteville, N.Y.)
|July 19, 2016
Summary
Researchers found differences in dopamine autoreceptor sensitivity between high and low alcohol-drinking mouse strains. Chronic ethanol exposure reduced dopamine synthesis, and lower dopamine activity correlated with increased alcohol consumption.
Area of Science:
- Neurobiology
- Neuropharmacology
- Addiction Research
Background:
- Alcoholism is a complex neuropsychiatric disease with significant public health implications.
- Understanding the neurobiological underpinnings of alcohol drinking is crucial for developing effective treatments.
- Preclinical models, particularly inbred mouse lines, offer valuable insights into individual differences in alcohol consumption.
Purpose of the Study:
- To investigate basal differences in dopamine system function between alcohol-preferring (C57BL/6J) and alcohol-avoiding (DBA/2J) mice.
- To determine the effects of chronic intermittent ethanol (CIE) exposure on dopamine synthesis and autoreceptor sensitivity.
- To explore the relationship between dopaminergic activity and alcohol consumption in a mouse model.
Main Methods:
- Assessed dopamine synthesis via L-aromatic acid decarboxylase inhibition and L-Dopa accumulation.
- Measured tyrosine hydroxylase activity using high-performance liquid chromatography.
- Utilized quinpirole to assess D2-type dopamine autoreceptor sensitivity.
- Administered chronic intermittent ethanol (CIE) exposure and withdrawal cycles.
- Analyzed dopamine and dopamine metabolite levels in recombinant inbred BXD mice.
Main Results:
- No significant basal differences in dopamine synthesis were found between C57BL/6J and DBA/2J mice in key brain regions.
- C57BL/6J mice exhibited greater quinpirole-induced inhibition of dopamine synthesis, indicating heightened presynaptic D2-autoreceptor sensitivity.
- Two cycles of CIE exposure led to attenuated baseline dopamine synthesis in the ventral striatum of C57BL/6J mice.
- In BXD mice, a higher dopamine/metabolite ratio (indicating lower dopaminergic activity) was positively correlated with alcohol drinking.
Conclusions:
- Dopamine synthesis and D2-autoreceptor function differ between high and low alcohol-drinking mouse strains.
- Chronic ethanol exposure can alter dopamine synthesis, potentially contributing to maladaptive drinking behaviors.
- Reduced dopaminergic activity is associated with increased alcohol consumption, suggesting a role for the dopamine system in alcohol preference.
