Studies at the behavioral and synaptic level show that effects of ethanol on the central nervous system can involve the opioid signaling system. These interactions may alter the function of a common downstream target. In this study, we examined Ca2+ channel function as a potential downstream target of interactions between ethanol and μ or κ opioid receptor signaling.
The studies were carried out in a model system, undifferentiated PC12 cells transfected with μ or κ opioid receptors. The PC12 cells express L-type Ca2+ channels, which were activated by K+ depolarization. Ca2+ imaging was used to measure relative Ca2+ flux during K+ depolarization and the modulation of Ca2+ flux by opioids and ethanol.
Ethanol, μ receptor activation, and κ receptor activation all reduced the amplitude of the Ca2+ signal produced by K+ depolarization. Pretreatment with ethanol or combined treatment with ethanol and μ or κ receptor agonists caused a reduction in the amplitude of the Ca2+ signal that was comparable to or smaller than that observed for the individual drugs alone, indicating an interaction by the drugs at a downstream target (or targets) that limited the modulation of Ca2+ flux through L-type Ca2+ channels.
hese studies provide evidence for a cellular mechanism that could play an important role in ethanol regulation of synaptic transmission and behavior through interactions with the opioid signaling.
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