Cook C D, Beardsley P M
Department of Pharmacology and Toxicology, Virginia Commonwealth University, Richmond, Virginia 23298-0613, USA.
Behav Pharmacol. 2004 Feb;15(1):65-74. doi: 10.1097/00008877-200402000-00008.
Mu opioid receptor agonists such as morphine stimulate the release of dopamine (DA) in various brain regions. These increases in DA are thought to be involved in some of the behavioral effects of mu agonists. The present study was designed to examine the modulatory actions of two D2/3 antagonists (nafadotride and eticlopride), the D2/3 partial agonist BP897, the D1/2 antagonist flupenthixol, and the D1 antagonist SCH23390 on the discriminative stimulus effects of the mu partial agonist nalbuphine and the higher-efficacy mu agonists heroin, methadone and morphine, in rats trained to discriminate heroin from water. Both nafadotride and eticlopride attenuated the effects of the mu agonists, whereas BP897 was effective against nalbuphine and partially effective against morphine. Flupenthixol attenuated the heroin-like discriminative stimulus effects of heroin and morphine, although not as completely as nafadotride or eticlopride. SCH23390 was least effective and produced little attenuation. These results demonstrate that the discriminative stimulus effects of mu agonists in rats are more readily attenuated by drugs that block D2-like, rather than D1-like, receptors.
μ阿片受体激动剂，如吗啡，可刺激多巴胺（DA）在大脑不同区域的释放。这些多巴胺的增加被认为与μ激动剂的某些行为效应有关。本研究旨在考察两种D2/3拮抗剂（萘法朵屈和依替必利）、D2/3部分激动剂BP897、D1/2拮抗剂氟哌噻吨以及D1拮抗剂SCH23390对μ部分激动剂纳布啡以及高效能μ激动剂海洛因、美沙酮和吗啡辨别刺激效应的调节作用，实验对象为经过训练能区分海洛因和水的大鼠。萘法朵屈和依替必利均减弱了μ激动剂的效应，而BP897对纳布啡有效，对吗啡部分有效。氟哌噻吨减弱了海洛因和吗啡类似海洛因的辨别刺激效应，尽管不如萘法朵屈或依替必利彻底。SCH23390效果最差，几乎没有减弱作用。这些结果表明，大鼠中μ激动剂的辨别刺激效应更容易被阻断D2类而非D1类受体的药物减弱。
