The effect of methadone on blood glucose, lipids and glucose-modulating hormones in methadone-dependent Wistar rats


A growing body of evidence indicates that opioids regulate mechanisms activated during the stress response. This study was aimed to investigate the effect of methadone dependency on blood glucose, lipids and glucose-modulating hormones in male and female Wistar rats.This study was performed on 40 Wistar rats weighing 150–350 g, in four methadone exposure and control groups of both males and females. All rats were weighed at the beginning and end of the study and their fasting blood glucose was measured using a glucometer. In order to induce addiction, methadone was injected intraperitoneal for 10 consecutive days at 5 mg/kg dose. The control group received the same volume of only normal saline. At the end of the study, the rats were sacrificed and their blood serum collected to measure cortisol, glucagon, adrenaline and lipid profile levels.There was a significant decrease in the mean final blood glucose of methadone-treated versus control male rats (p = 0.02). There was no significant glucose difference, however, in female rats. Furthermore, a decrease in the mean serum levels of triglyceride, cortisol, and adrenaline occurred in male rats of methadone-dependent compared with control animals, but there was no significant difference in these values in female rats. Our results showed that methadone significantly reduced serum glucose as well as triglyceride levels only in male rats, this being associated with a reduction in the level of counter-regulating hormones of carbohydrate metabolism. Changes in lipid profiles, however, occurred independently of gender.

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Adrenocorticotropic hormone


Central nervous system


Corticotrophin releasing hormone


Follicular stimulating hormone


Hepatitis C virus


Hepatitis B virus




High density lipoprotein


Low density lipoprotein


Luteinizing hormone


Methadone maintenance treatment


Standard deviation


The United Nations’ Office on Drugs and Crime


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The authors would like to thank the Vice Chancellor for the Research and Technology of the Birjand University of Medical Sciences for funding this study (the research Project No. 455381.)

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Correspondence to Zoya Tahergorabi.

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Tahergorabi, Z., Rahmani, H., Williams, J. et al. The effect of methadone on blood glucose, lipids and glucose-modulating hormones in methadone-dependent Wistar rats. Toxicol Res. 36, 221–226 (2020).

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  • Methadone
  • Glucose-modulating hormones
  • Wistar rats
  • Blood glucose