Melchiorri P, Maritati M, Negri L, Erspamer V
Institute of Medical Pharmacology, University La Sapienza, Rome, Italy.
Proc Natl Acad Sci U S A. 1992 May 1;89(9):3696-700. doi: 10.1073/pnas.89.9.3696.
In experiments to evaluate responses to the activation of cerebral delta-opioid receptors, repeated daily injection of the selective delta-opioid agonist Tyr-D-Ala-Phe-Glu-Val-Val-Gly-NH2 ([D-Ala2]deltorphin II) into rat brain resulted in the development of tolerance, whereas repeated daily injection or continuous infusion of morphine resulted in sensitization to the behavioral activating effects of the delta-opioid agonist. Although the rats did not modify their spontaneous locomotor activity after morphine withdrawal, they became markedly hyperresponsive to the locomotor and stereotypy-producing effects of a challenge dose of the delta-opioid agonist. Sensitization to activation of delta-opioid receptors persisted for at least 60 days after discontinuing morphine treatment. These results show that the development of tolerance and long-term sensitization to opioids involves delta-opioid as well as mu-opioid receptors.
在评估对脑内δ-阿片受体激活反应的实验中，每天重复向大鼠脑内注射选择性δ-阿片激动剂酪氨酰-D-丙氨酰-苯丙氨酰-谷氨酰胺-缬氨酰-缬氨酰-甘氨酰胺（[D-Ala2]强啡肽II）会导致耐受性的产生，而每天重复注射或持续输注吗啡则会导致对δ-阿片激动剂行为激活作用的敏化。尽管大鼠在吗啡戒断后并未改变其自发运动活性，但它们对挑战剂量的δ-阿片激动剂的运动和刻板行为产生作用变得明显反应过度。在停止吗啡治疗后，对δ-阿片受体激活的敏化持续至少60天。这些结果表明，对阿片类药物耐受性和长期敏化的产生涉及δ-阿片受体以及μ-阿片受体。
