preproenkephalin and Drug-Overdose

To determine whether there are factors during apparent rapid heroin overdose death that affect agonal state and thus brain pH (index of hypoxia) that can influence neurobiological systems linked to drug abuse.. Brain specimens and autopsy/medical reports were investigated in subjects dying from heroin overdose (n=70) and compared to normal controls (n=45) as well as suicide victims (n=31) with a documented rapid cause of death. Detailed autopsy material was characterized as to positive and negative respiratory distress in relation to brain pH; drug toxicity and other demographic information was also evaluated. In situ hybridization histochemistry was used to study mRNA expression levels of dopamine (e.g., D2 receptor, dopamine transporter) and opioid (e.g., proenkephalin) related markers in various structures in relation to brain pH.. Brain pH was generally reduced in heroin overdose cases versus normal and suicide subjects. There was, however, significant variation in heroin overdose deaths related to differences in respiratory distress that differentially altered brain pH levels. Various factors such as vomit inhalation, resuscitation, pulmonary embolism and suffocation contributed to positive respiratory distress. Elevated brain pH was observed in heroin overdose with positive alcohol toxicity suggesting potentiated alcohol-induced rapidity of heroin deaths. mRNA expression levels of the dopamine-related genes and proenkephalin were positively correlated with brain pH.. Respiratory distress contributes to variations in the acute agonal state during heroin overdose death that differentially alters brain pH levels and significantly impacts mRNA levels. Such findings should be considered for postmortem molecular/neurochemical neurobiological studies of opiate abusers.

Topics: Adolescent; Adult; Aged; Autopsy; Brain Chemistry; Central Nervous System Depressants; Drug Overdose; Enkephalins; Ethanol; Female; Heroin; Humans; Hydrogen-Ion Concentration; In Situ Hybridization; Male; Middle Aged; Prevalence; Protein Precursors; Receptors, Dopamine D2; Respiratory Distress Syndrome; RNA, Messenger; Suicide