Carlson K R, Seeger T F
Pharmacol Biochem Behav. 1982 Jan;16(1):119-24. doi: 10.1016/0091-3057(82)90022-3.
We examined the hypothesis that opiates act as dopamine (DA) receptor-blocking agents thereby inducing a compensatory increase in DA receptor density during chronic administration, and that increased receptor density could account for the behavioral hypersensitivity to DA agonists seen after treatment with opiates. Morphine and methadone did not inhibit the specific binding of 3H-spiroperidol to DA receptors in vitro, nor did they decrease affinity or apparent receptor density in the striatum when administered acutely in vivo in behaviorally effective doses. In contrast, neuroleptics had the expected inhibitory effect in both these experiments. Stereotypy and locomotion in response to apomorphine were measured before and after a 3-week treatment with saline or methadone. About half the methadone-treated rats showed significant increases over predrug baselines in stereotypy or locomotion, as did a few saline-treated animals. However, in those animals showing enhanced stereotypy or locomotion, DA receptor density was not elevated in striatum or mesolimbic areas respectively. These results indicate that opiates do not act as antagonists at DA receptor sites, and that changes in DA receptor density cannot account for opiate-induced behavioral hypersensitivity.
阿片类药物作为多巴胺（DA）受体阻断剂，从而在长期给药期间诱导DA受体密度的代偿性增加，并且增加的受体密度可以解释在用阿片类药物治疗后观察到的对DA激动剂的行为超敏反应。吗啡和美沙酮在体外并未抑制3H-螺哌啶醇与DA受体的特异性结合，并且当以行为有效剂量在体内急性给药时，它们也不会降低纹状体中的亲和力或表观受体密度。相比之下，抗精神病药物在这两个实验中都有预期的抑制作用。在用生理盐水或美沙酮进行3周治疗之前和之后，测量了对阿扑吗啡的刻板行为和运动。约一半接受美沙酮治疗的大鼠在刻板行为或运动方面比给药前基线有显著增加，一些接受生理盐水治疗的动物也是如此。然而，在那些表现出增强的刻板行为或运动的动物中，纹状体或中脑边缘区域的DA受体密度并未升高。这些结果表明，阿片类药物在DA受体位点并非作为拮抗剂起作用，并且DA受体密度的变化不能解释阿片类药物诱导的行为超敏反应。
