Centre National de la Recherche Scientifique, Unité Mixte de Recherche 8206, Paris, France.
Psychopharmacology (Berl). 2011 Jul;216(2):297-303. doi: 10.1007/s00213-011-2223-6. Epub 2011 Feb 22.
Behavioral sensitization induced by repeated morphine administrations may depend on patterns of administration. However, neurobiological mechanisms involved in this sensitization are largely unknown.
We compared the effects of intermittent (20 mg/kg, once daily for 7 days) and chronic (escalating doses from 5 to 40 mg/kg, three times a day for 5 days) morphine treatments in mice on locomotor activity. We also quantified, by autoradiography, mu opioid receptor (MOR) in ventral tegmental area (VTA), dopamine D1 (D1R) and D2 (D2R) receptors in striatum.
Whereas the intermittent treatment led to a long-term sensitization to locomotor effects of morphine [until withdrawal day (WD) 14], the chronic treatment induced a tolerance (WD1) followed by a transient sensitization (WD14). Binding studies demonstrated a decrease of MOR in VTA at WD1 for the chronic treatment. In contrast, striatal D1R level was decreased at WD1, and increased at WD14 for the chronic treatment. For the D2R, we observed a decrease from WD1 to WD14 for the intermittent treatment and an increase at WD1 followed by a decrease at WD14 for the chronic treatment.
These results demonstrate that chronic and intermittent morphine treatments could induce different behavioral adaptations that could be explained in part by distinct changes occurring in dopamine and opioid systems.
反复给予吗啡可能会导致行为敏感化，这取决于给药方式。然而，这种敏感化所涉及的神经生物学机制在很大程度上尚不清楚。
我们比较了间歇性（20mg/kg，每天一次，共 7 天）和慢性（递增剂量从 5 到 40mg/kg，每天三次，共 5 天）吗啡处理在小鼠自主活动中的影响。我们还通过放射自显影技术定量检测了腹侧被盖区（VTA）中的μ阿片受体（MOR）、纹状体中的多巴胺 D1（D1R）和 D2（D2R）受体。
尽管间歇性治疗导致了对吗啡的长期敏感化（直到停药日（WD）14 天），但慢性治疗导致了对吗啡的耐受性（WD1），随后是短暂的敏感化（WD14）。结合研究表明，慢性治疗在 WD1 时 VTA 中的 MOR 减少。相比之下，慢性治疗在 WD1 时纹状体中的 D1R 水平降低，而在 WD14 时增加。对于 D2R，我们观察到间歇性治疗在 WD1 到 WD14 期间减少，而慢性治疗在 WD1 时增加，然后在 WD14 时减少。
这些结果表明，慢性和间歇性吗啡处理可能会引起不同的行为适应，这可以部分解释为多巴胺和阿片系统发生的不同变化。
