Time‐dependent regional brain distribution of methadone and naltrexone in the treatment of opioid addiction

Opioid addiction is a serious public health concern with severe health and social implications; therefore, extensive therapeutic efforts are required to keep users drug free. The two main pharmacological interventions, in the treatment of addiction, involve management with methadone an mu (μ)‐opioid agonist and treatment with naltrexone, μ‐opioid, kappa (κ)‐opioid and delta (δ)‐opioid antagonist. MET and NAL are believed to help individuals to derive maximum benefit from treatment and undergo a full recovery. The aim of this study was to determine the localization and distribution of MET and NAL, over a 24‐hour period in rodent brain, in order to investigate the differences in their respective regional brain distributions. This would provide a better understanding of the role of each individual drug in the treatment of addiction, especially NAL, whose efficacy is controversial. Tissue distribution was determined by using mass spectrometric imaging (MSI), in combination with quantification via liquid chromatography tandem mass spectrometry. MSI image analysis showed that MET was highly localized in the striatal and hippocampal regions, including the nucleus caudate, putamen and the upper cortex. NAL was distributed with high intensities in the mesocorticolimbic system including areas of the cortex, caudate putamen and ventral pallidum regions. Our results demonstrate that MET and NAL are highly localized in the brain regions with a high density of μ‐receptors, the primary sites of heroin binding. These areas are strongly implicated in the development of addiction and are the major pathways that mediate brain stimulation during reward. MSI analysis showed that MET and NAL are highly localized in the brain regions with a high density of MU‐opioid receptors, the primary sites of heroin binding. MET was highly localized in the striatal and hippocampal regions, including the nucleus caudate, putamen and the upper cortex. NAL was distributed with high intensities in the mesocorticolimbic system including areas of the cortex, caudate putamen and ventral pallidum regions. These areas are involved in the development of addiction and are the major pathways that mediate brain stimulation during reward.