Dissecting the Distribution of Heroin in the Brain

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A UKZN PhD study investigated the distribution of heroin as well as opioids, opioid agonist and antagonists and their localisation in the brain using Mass Spectrometry Imaging (MSI) for the first time.

MSI offers an advantage over existing imaging technologies such as positron emission tomography (PET) or Single, Photon Emission Computed Tomography (SPECT) since it eliminates the need for radioactive labels, a chemical compound in which one or more atoms have been replaced by a radionuclide so by virtue of its radioactivedecay it can be used to explore the mechanism of chemical reactions by tracing the path that the radioisotope follows from reactants to products.

Titled: Regional Brain Distribution and Localisation of Herion and Opioid Addiction Treatment Drugs via Mass Spectrometry, the study was conducted by Dr Bilen Gebrekidan Teklezgi under the supervision of Professors T Govender, HG Gruger, N Gopal and Dr S Baijnath.

According to Teklezgi, the impact of drug abuse and its health and social consequences continue to be a public health crisis. ‘Heroin is a commonly abused illicit opioid drug and leads to addiction; a chronic brain disease which requires psychological and pharmaceutical intervention. Opioid induced overdose deaths accounts for the death of approximately 69 000 people worldwide each year,’ she said.

She said the evaluation of the distribution and localisation of opioid drugs, as well as their treatment to addiction, in the brain is of major significance. 

The study employed MSI and liquid chromatography mass spectrometry (LC-MS/MS) for quantification to investigate 6-MAM (heroin’s major metabolite) distribution profile over time in the brain; determine and compare the localisation of methadone and naltrexone; as well as determine and compare the regional distribution of 6-MAM and 6-MAM post naloxone treatment to evaluate the ability of naloxone to displace 6-MAM in the brain of Spraque-Dawley rats. ‘MSI analysis of the brain sections showed region-specific localisation images of 6-MAM, methadone, naltrexone and naloxone with high intensities of these drugs in the mesocorticolimbic system which is involved in reward perception and thalamus-hypothalamus of the brain regions responsible for motivation and energy regulation,’ explained Teklezgi. 

She said the findings were in correlation with the distribution of opioid receptors in the brain as reported in literature. ‘MSI study demonstrated a time-dependent distribution in the levels of 6-MAM, methadone and naltrexone at various time points. In addition, MSI experiments showed the ability of naloxone to displace 6-MAM, at specific sites in the brain,’ she said.

Teklezgi plans to continue with research focusing on addiction and behaviour from a public health perspective.

Words: Nombuso Dlamini 

Photograph: Rajesh Jantilal