Cocaine added to heroin fails to affect heroin-induced brain hypoxia

Thomas, Seddon Y.; Perekopskiy, David; Kiyatkin, Eugene A.

doi:10.1016/j.brainres.2020.147008

Cited by 9 publications

(7 citation statements)

References 18 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The 1.0 mg/kg for cocaine is an optimal dose maintaining rat self-administration 21 – 23 and well within the range of human consumption. As shown previously, cocaine at this dose modestly increases NAc oxygen levels 14 , 16 . 0.1 mg/kg of heroin is an optimal dose maintaining rat self-administration 22 , 24 ; with 0.4 mg/kg corresponding to upper limits of human consumption.…”

Section: Methodssupporting

confidence: 85%

“…While the latter factors could play a role in post-hypoxic brain oxygen increase, skin vasoconstriction induced by this drug 46 is another contributor. Interestingly, heroin at a lower dose (0.05 mg/kg), which is still in the reinforcing range, induces only a weak, monophasic and more tonic increases in NAc oxygen 16 that could be related to drug-induced peripheral vasoconstriction. Therefore, brain hypoxia resulting from respiratory depression is an effect typical only for relatively large heroin doses.…”

Section: Discussionmentioning

confidence: 98%

“…In addition to physiological stimuli, we examined the relationships between central and peripheral oxygen responses induced by two prominent drugs of abuse: cocaine and heroin. While intravenous (iv) cocaine passively injected at low self-administering doses modestly increases NAc oxygen levels 15 , 16 , it also induces peripheral vasoconstriction 17 suggesting its possible contribution to brain oxygen increases. In contrast to sensory stimuli and cocaine, heroin modestly increases brain oxygen levels at low reinforcing doses but induces a dose-dependent decrease followed by rebound-like increase at higher drug doses 16 , 18 .…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Relationships between oxygen changes in the brain and periphery following physiological activation and the actions of heroin and cocaine

Thomas

Curay

Kiyatkin

2021

Sci Rep

Self Cite

View full text Add to dashboard Cite

Using two-sensor electrochemical recordings in freely moving rats, we examined the relationship between physiological and drug-induced oxygen fluctuations in the brain and periphery. Animals chronically implanted with oxygen sensors in the nucleus accumbens (NAc) and subcutaneous (SC) space were subjected to several mildly arousing stimuli (sound, tail-pinch and social interaction) and intravenous injections of cocaine and heroin. Arousing stimuli induced rapid increases in NAc oxygen levels followed by and correlated with oxygen decreases in the SC space. Therefore, cerebral vasodilation that increases cerebral blood flow and oxygen entry into brain tissue results from both direct neuronal activation and peripheral vasoconstriction, which redistributes arterial blood from periphery to the brain. The latter factor could also explain a similar pattern of oxygen responses found in the substantia nigra reticulata, suggesting hyperoxia as a global phenomenon with minor structural differences during early time intervals following the stimulus onset. While arousing stimuli and cocaine induced similar oxygen responses in the brain and SC space, heroin induced a biphasic down-up brain oxygen fluctuation associated with a monophasic oxygen decrease in the SC space. Oxygen decreases occurred more rapidly and stronger in the SC space, reflecting a drop in blood oxygen levels due to respiratory depression.

show abstract

Section: Methodssupporting

confidence: 85%

Section: Discussionmentioning

confidence: 98%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Relationships between oxygen changes in the brain and periphery following physiological activation and the actions of heroin and cocaine

Thomas

Curay

Kiyatkin

2021

Sci Rep

Self Cite

View full text Add to dashboard Cite

show abstract

“…Acute and chronic drug assumption leads to several microscopic alterations that may be helpful to recognize and suspect drug-related deaths. Hemorrhagic protein-rich pulmonary edema, brain edema, diffuse stasis, and acute emphysema are frequent findings in drugs intoxication characterized by acute respiratory function impairment [23,24]. The skin samples of injection marks need to be sampled for histological examination.…”

Section: Discussionmentioning

confidence: 99%

A Forensic Diagnostic Algorithm for Drug-Related Deaths: A Case Series

Argo

Zerbo

Buscemi

et al. 2022

Toxics

View full text Add to dashboard Cite

The best evidence provided in the literature worldwide suggests the importance of harmonizing the investigation in drug-related fatalities. In this study, the application of a multidisciplinary approach in eight cases of drug-related deaths is presented. Although death scene findings could be highly suggestive of drug intoxication, external examination and toxicological screening test alone are insufficient. There are several variables, and it is not always easy to give the proper interpretation of the drug detection. A complete autopsy is necessary to correctly complete organ and tissues sampling for further histological and toxicological studies and obtain body fluids. The use of peripheral blood is recommended to avoid artifacts. The collection of many specimens is warranted to get more responses. The sampling aims to provide a picture of the distribution of the substance in the body. The sample and the selection of the drugs and the matrices to investigate are case-dependent. The presented diagnostic algorithm provides the coroner with all the elements to investigate drug-related deaths and cooperate with toxicologists. Toxicological forensic diagnosis is still extremely heterogeneous in regional and national contexts. Funding for method development, research, networking, facilities, and technologies improvement is mandatory to standardize the toxicological investigation.

show abstract

“…When administered to rodents, cocaine increases oxygen entry into brain tissue by 10 to 15%. 17 Thomas et al 18 studied whether cocaine is able to reverse the decrease in brain oxygen levels that occurs after heroin administration. To determine the oxygen levels, oxygen sensors were placed in the nucleus accumbens, as a measure of the functional output of breathing activity.…”

Section: Cocainementioning

confidence: 99%

Advances in Reversal Strategies of Opioid-induced Respiratory Toxicity

et al. 2021

View full text Add to dashboard Cite

Opioids may produce life-threatening respiratory depression and death from their actions at the opioid receptors within the brainstem respiratory neuronal network. Since there is an increasing number of conditions where the administration of the opioid receptor antagonist naloxone is inadequate or undesired, there is an increased interest in the development of novel reversal and prevention strategies aimed at providing efficacy close to that of the opioid receptor antagonist naloxone but with fewer of its drawbacks such as its short duration of action and lesser ability to reverse high-affinity opioids, such as carfentanil, or drug combinations. To give an overview of this highly relevant topic, the authors systematically discuss predominantly experimental pharmacotherapies, published in the last 5 yr, aimed at reversal of opioid-induced respiratory depression as alternatives to naloxone. The respiratory stimulants are discussed based on their characteristics and mechanism of action: nonopioid controlled substances (e.g., amphetamine, cannabinoids, ketamine), hormones (thyrotropin releasing hormone, oxytocin), nicotinic acetylcholine receptor agonists, ampakines, serotonin receptor agonists, antioxidants, miscellaneous peptides, potassium channel blockers acting at the carotid bodies (doxapram, ENA001), sequestration techniques (scrubber molecules, immunopharmacotherapy), and opioids (partial agonists/antagonists). The authors argue that none of these often still experimental therapies are sufficiently tested with respect to efficacy and safety, and many of the agents presented have a lesser efficacy at deeper levels of respiratory depression, i.e., inability to overcome apnea, or have ample side effects. The authors suggest development of reversal strategies that combine respiratory stimulants with naloxone. Furthermore, they encourage collaborations between research groups to expedite development of viable reversal strategies of potent synthetic opioid-induced respiratory depression.

show abstract

Cocaine added to heroin fails to affect heroin-induced brain hypoxia

Cited by 9 publications

References 18 publications

Relationships between oxygen changes in the brain and periphery following physiological activation and the actions of heroin and cocaine

Relationships between oxygen changes in the brain and periphery following physiological activation and the actions of heroin and cocaine

A Forensic Diagnostic Algorithm for Drug-Related Deaths: A Case Series

Advances in Reversal Strategies of Opioid-induced Respiratory Toxicity

Contact Info

Product

Resources

About