期刊
ACS CHEMICAL NEUROSCIENCE
卷 10, 期 8, 页码 3409-3414出版社
AMER CHEMICAL SOC
DOI: 10.1021/acschemneuro.9b00305
关键词
opioid; metabolism; voltammetry; vasoconstriction; vasodilation; brain hypoxia; respiratory depression; diacetylmorphine
资金
- Intramural Research Program of the NIH, NIDA
Heroin rapidly enters the CNS but is quickly metabolized into 6-monoacetylmorphine (6-MAM) and then morphine. Although morphine is often thought to mediate heroin's neural effects, pharmacokinetic data question this view. To further understand the effects of heroin and its metabolites, oxygen sensors were used to examine changes in nucleus accumbens (NAc) oxygen levels. Heroin, 6-MAM, and morphine were all administered intravenously at two human-relevant doses (0.25 mu mol/kg and 0.98 mu mol/kg) in freely moving rats. Intravenous heroin induced a biphasic change in NAc oxygen, with a decrease resulting from respiratory depression and an increase resulting from cerebral vasodilation. 6-MAM caused similar but more rapid and slightly weaker effects than heroin. The stronger response to heroin can be primarily attributed to heroin's permeability and metabolism resulting in more 6-MAM in the brain. Morphine only induced weak increases in NAc oxygen. Therefore, it appears that 6-MAM is the major contributor to acute neural effects induced by iv heroin.
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