Differential effects of methadone and buprenorphine on the response of D2/D3 dopamine receptors in adolescent mice

作者：Barwatt J William; Hofford Rebecca S; Emery Michael A; Bates M L Shawn; Wellman Paul J; Eitan Shoshana^*

来源：Drug and Alcohol Dependence, 2013, 132(3): 420-426.

DOI：10.1016/j.drugalcdep.2013.07.016

• Addiction
• Dependence
• Drugs of abuse
• Maintenance treatment
• Opioid
• Pain management

Background: There is a lack of studies that examine the effects of opioid maintenance drugs on the developing adolescent brain, limiting the ability of physicians to conduct a science-based risk assessment on the appropriateness of these treatments for that age group. Our recent observations indicate higher potential risks in repeated exposure to morphine during adolescence, specifically to the D2/D3 dopamine receptors' signaling. Disturbances in dopaminergic signaling could have broader implications for long-term mental health. Thus, this study examined whether buprenorphine and methadone differentially alter the responses of the D2/D3 dopamine receptors in adolescents.
Methods: Adolescent mice were orally administered buprenorphine (0.1-0.4 mg/kg), methadone (25-100 mg/kg), or saline once daily for 6 days. Two hours or three days later,. the mice were tested for their locomotor response to 10 mg/kg quinpirole, a D2/D3 dopamine receptor agonist.
Results: Buprenorphine-treated adolescent mice did not significantly differ from control drug-naive animals in their response to quinpirole. However, an enhanced response was observed in methadone-treated adolescent animals. This enhanced locomotion was significantly higher two hours following the final dose of methadone, as compared to three days afterwards.
Conclusions: This study suggests that exposure to various opioids carries differential probabilities of altering the highly sensitive neurochemistry of adolescent brains. Methadone exposure disturbs the D2-like receptor's response, indicating a potential risk in administering methadone to adolescents (either for the treatment of opioid dependency/abuse or for pain management). In contrast, buprenorphine appears to have a significantly lower effect on the behavioral sensitivity of D2/D3 dopamine receptors in adolescents.

• 出版日期2013-10-1