Wennemer H K, Kornetsky C
Department of Pharmacology, University of New England, 11 Hills Beach Road, Biddeford, ME 04005, USA.
Psychopharmacology (Berl). 1999 Sep 1;146(1):19-23. doi: 10.1007/s002130051083.
Repeated high doses of morphine in the rat cause stereotypic gnawing behavior that can be re-expressed by a low dose of morphine weeks and even months after the initial treatment. The determination of the role of serotonin in this sensitized morphine-induced behavior has both empirical and theoretical relevance.
To determine whether the serotonin-reuptake blocker fluoxetine will block the development and/or the expression of this opiate-induced stereotypy.
Rats were given four 10-mg/kg injections of morphine alone or with 5.0 mg/kg fluoxetine over a 36-h period. At weekly intervals for 6 weeks after the last of the sensitizing morphine doses, all rats were challenged with 4.0 mg/kg morphine. At week 2 and week 4, however, the morphine was co-administered with fluoxetine.
Fluoxetine completely blocked the expression of the morphine-induced stereotypy; however, when the morphine/fluoxetine-treated rats were challenged with morphine alone, they expressed similar degrees of stereotypy as the rats that initially only received morphine.
The results indicate that increasing synaptic serotonin will block the expression but not the development of sensitization to the oral stereotypic effects of repeated high doses of morphine. Also, despite the complete blocking of the morphine effect by fluoxetine during the sensitization phase, the presence of significant biting by these rats during the challenge with morphine alone argues that conditioning factors are not a necessary component for the morphine sensitization to develop.
在大鼠中反复给予高剂量吗啡会导致刻板啃咬行为，在初始治疗数周甚至数月后，低剂量吗啡可再次引发该行为。确定5-羟色胺在这种致敏性吗啡诱导行为中的作用具有实验和理论意义。
确定5-羟色胺再摄取阻滞剂氟西汀是否会阻断这种阿片类药物诱导的刻板行为的发展和/或表达。
在36小时内，给大鼠单独注射四次10毫克/千克的吗啡，或与5.0毫克/千克的氟西汀联合注射。在最后一次致敏性吗啡剂量后的6周内，每周对所有大鼠用4.0毫克/千克的吗啡进行激发试验。然而，在第2周和第4周，吗啡与氟西汀联合给药。
氟西汀完全阻断了吗啡诱导的刻板行为的表达；然而，当用吗啡/氟西汀治疗的大鼠单独用吗啡激发时，它们表现出与最初只接受吗啡的大鼠相似程度的刻板行为。
结果表明，增加突触5-羟色胺会阻断对反复高剂量吗啡口服刻板效应的致敏表达，但不会阻断其发展。此外，尽管在致敏阶段氟西汀完全阻断了吗啡的作用，但这些大鼠在单独用吗啡激发时出现明显咬啮行为，这表明条件因素不是吗啡致敏发展的必要组成部分。
