Cooper D O, Carlson K R, McKearney J W
Pharmacol Biochem Behav. 1985 Sep;23(3):349-54. doi: 10.1016/0091-3057(85)90005-x.
Male rats of the F-344 and BUF inbred strains were given free access to a 10% sucrose solution containing 0.5 mg/ml morphine sulfate (controls received sucrose only) as their sole source of fluids. The daily intake of morphine averaged 101 +/- 13 mg/kg. After 18 days on this regimen, animals were sacrificed and assayed for 3H-clonidine (alpha-2 adrenergic), 3H-dihydroalprenolol (DHA, beta 1 and 2 adrenergic) and 3H-spiperone (SPD, 5-HT2 and D2) binding in several brain regions. In the absence of morphine treatment, BUF rats displayed higher levels of SPD binding in brainstem, as compared with the F-344 strain. In contrast, untreated F-344 rats exhibited higher levels of DHA binding in hypothalamus and SPD binding in striatum than BUF rats. Chronic morphine resulted in an increase in clonidine and DHA binding in the brainstem and hippocampus respectively of BUF, but not F-344 rats, suggesting a greater sensitivity of adrenergic function to opiate treatment in the BUF strain. The two strains differed qualitatively in the effect of morphine on striatal SPD binding, with BUF rats exhibiting a decrease, and F-344 rats an increase. The one consistent change observed in both strains was a quantitatively similar increase in hippocampal SPD binding after chronic morphine. The results demonstrate that despite strain-dependent differences in binding characteristics, chronic morphine elicits a strain-independent alteration in hippocampal 5-HT2 binding. On the basis of these preliminary findings, it may be speculated that this particular neurochemical consequence contributes to morphine-induced behaviors which are observed independent of rat strain.
将F-344和BUF近交系雄性大鼠自由饮用含0.5mg/ml硫酸吗啡的10%蔗糖溶液(对照组仅饮用蔗糖)作为唯一的液体来源。吗啡的日均摄入量平均为101±13mg/kg。在该方案实施18天后,处死动物并检测几个脑区中3H-可乐定(α-2肾上腺素能)、3H-二氢阿普洛尔(DHA,β1和β2肾上腺素能)和3H-螺哌隆(SPD,5-HT2和D2)的结合情况。在未进行吗啡处理时,与F-344品系相比,BUF大鼠脑干中的SPD结合水平较高。相反,未处理的F-344大鼠下丘脑的DHA结合水平和纹状体的SPD结合水平高于BUF大鼠。慢性吗啡导致BUF大鼠脑干和海马体中可乐定和DHA结合分别增加,但F-344大鼠未出现这种情况,这表明BUF品系中肾上腺素能功能对阿片类药物治疗的敏感性更高。吗啡对纹状体SPD结合的影响在两个品系中存在质的差异,BUF大鼠表现为下降,而F-344大鼠表现为增加。在两个品系中观察到的一个一致变化是慢性吗啡处理后海马体SPD结合在数量上有相似的增加。结果表明,尽管结合特征存在品系依赖性差异,但慢性吗啡会引起海马体5-HT2结合的品系非依赖性改变。基于这些初步发现,可以推测这种特定的神经化学后果促成了与大鼠品系无关的吗啡诱导行为。