title: Up-regulation of monoamine oxidase activity in the striatum of rats following chronic treatment of thienorphine.
abstract: Thienorphine is a new, non-selective partial agonist of opioid receptors. In our previous study using microdialysis, thienorphine persistently increased the levels of 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) in the striatum of rats, without affecting the level of dopamine. This finding suggested that monoamine oxidase (MAO) activity in the striatum of rats increased by chronic thienorphine treatment. In the present study, we investigated whether chronic treatment of thienorphine affected MAO activity in the striatum of rats compared with morphine. Rats were treated subcutaneously (three times/day) with either saline (control), morphine, thienorphine, or a pre-treatment of thienorphine followed by morphine, for 3 or 5 continuous days. A 20-min naloxone challenge given to a sub-group of animals from each group occurred at the end of their 5-day treatment. The results showed that repeated administration of thienorphine significantly elevated MAO activity in the striatum, thus restoring MAO activity, which was inhibited by chronic morphine treatment. These results suggest that increased activity of MAO in the striatum may accelerate the metabolism of dopamine, leading to the elevations of DOPAC and HVA. Furthermore, these findings implicate the involvement of MAO in the pharmacological characteristics of thienorphine.
authors.affiliation: Beijing Institute of Pharmacology & Toxicology, 27th Taiping Road, Beijing 100850, China.
authors.forename: Zheng
authors.initials: Z
authors.lastname: Yong
authors.forename: Lingdi
authors.initials: L
authors.lastname: Yan
authors.forename: Xiao
authors.initials: X
authors.lastname: Wang
authors.forename: Ruibin
authors.initials: R
authors.lastname: Su
authors.forename: Zehui
authors.initials: Z
authors.lastname: Gong
mesh_terms: D000701:Analgesics, Opioid / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D002047:Buprenorphine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology; D003342:Corpus Striatum / Q000187:drug effects* / Q000201:enzymology; D004298:Dopamine / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D054333:Drug Partial Agonism; D007279:Injections, Subcutaneous; D008297:Male; D008995:Monoamine Oxidase / Q000378:metabolism*; D009020:Morphine / Q000494:pharmacology*; D009270:Naloxone / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D011957:Receptors, Opioid / Q000819:agonists; D013997:Time Factors; D015854:Up-Regulation
chemical_list: D000701:Analgesics, Opioid; D011957:Receptors, Opioid; C512397:thienorphine; D009270:Naloxone; D002047:Buprenorphine; D009020:Morphine; D008995:Monoamine Oxidase; D004298:Dopamine