Effects of alcohol on brain oxygenation and brain hypoxia induced by intravenous heroin. (1st October 2021)

• Record Type: Journal Article
• Authors: Thomas, Shruthi A.; Curay, Carlos M.; Kiyatkin, Eugene A.
• Is Part Of: Neuropharmacology. Volume 197(2021)
• Publication Date: 2021-10-01
• Subjects: Brain oxygen -- Brain temperature -- Opioid drugs -- Neural activation -- Peripheral vasoconstriction -- Central vasodilation -- Rats; ANOVA analysis of variance -- CNS central nervous system -- ig intragastric -- iv intravenous -- LD50 the dose of a toxic substance that is sufficient to kill 50% of a population of animals -- NAc nucleus accumbens; Neuropsychopharmacology -- Periodicals; Autonomic Agents -- Periodicals; Neuropsychopharmacologie -- Périodiques; Neuropsychopharmacology; Periodicals; Electronic journals; 615.78
• DOI: 10.1016/j.neuropharm.2021.108713
• Languages: English
• ISSNs: 0028-3908

Abstract

Abstract: Alcohol is the most commonly used psychoactive drug, often taken in conjunction with opioid drugs. Since both alcohol and opioids can induce CNS depression, it is often assumed that alcohol potentiates the known hypoxic effects of opioid drugs. To address this supposition, we used oxygen sensors to examine the effects of alcohol on brain oxygenation and hypoxic responses induced by intravenous heroin in awake, freely moving rats. To eliminate robust sensory effects of alcohol following its oral or intraperitoneal delivery, alcohol was administered directly into the stomach via chronically implanted intragastric catheters at human relevant doses. Alcohol delivered at a 0.5 g/kg dose did not affect brain oxygen levels, except for a weak transient increase during drug delivery. This phasic oxygen increase was stronger at a 2.0 g/kg alcohol dose and followed by a weaker tonic increase. Since alcohol absorption from intragastric delivery is much slower and more prolonged than with intraperitoneal or intravenous injections, the rapid rise of brain oxygen levels suggests that alcohol has a direct action on sensory afferents in the stomach well before the drug physically reaches brain tissue via circulation. Despite slow tonic increases in brain oxygen, alcohol at the 2.0 g/kg dose strongly potentiates heroin-induced oxygen responses, increasing both the magnitude and duration of oxygen decrease. Therefore, under the influence of alcohol, the use of opioid drugs becomes much more dangerous, increasing brain hypoxia and enhancing the probability of serious health complications, including coma and death. Highlights: Electrochemical sensors were used to monitor drug-induced changes in brain oxygen. Alcohol was delivered to rats intragastrically under stress-free conditions. Alcohol during delivery induced phasic oxygen increase followed by tonic increase. Alcohol strongly potentiated heroin-induced brain oxygen decreases. The danger of opioid drugs is dramatically enhanced under the influence of alcohol.