Gralewicz Sławomir
Nofer Institute of Occupational Medicine, Department of Toxicology and Carcinogenesis, 8 Teresy St., 90-95 Łódz, Poland.
Acta Neurobiol Exp (Wars). 2002;62(2):93-8. doi: 10.55782/ane-2002-1425.
Earlier experiments have revealed that rats treated with a single dose of chlorphenvinphos (CVP), an irreversible acetylcholinesterase inhibitor, are hyposensitive to amphetamine (AMPH) given three weeks after CVP. Exposure to CVP results in an excess of acetylcholine with subsequent overactivation of the nicotinic as well as muscarinic cholinergic receptors. The purpose of the present experiment was to find out whether a selective activation of muscarinic receptors could induce behavioral hyposensitivity to AMPH. To attain this purpose, male rats were pretreated once with 0.00, 0.135, 0.27 or 0.55 mg/kg of oxotremorine, a muscarinic agonist, and challenged 15 days later with 1.0 mg/kg dose of AMPH. The pre- and postinjection open-field behavior of the rats was tested with the use of a computerized set of activity meters. The testing revealed that in oxotremorine pretreated animals the behavioral response to AMPH, i.e. increase in the ambulatory activity, was not diminished but, to the contrary, it was augmented. This effect was dose-dependent, being most pronounced in rats given the 0.55 mg/kg of oxotremorine. The possible cause of the difference between the effect of CVP and oxotremorine is discussed.
早期实验表明，用单剂量的毒死蜱（CVP，一种不可逆的乙酰胆碱酯酶抑制剂）处理过的大鼠，在CVP给药三周后对苯丙胺（AMPH）反应迟钝。接触CVP会导致乙酰胆碱过量，随后烟碱型和毒蕈碱型胆碱能受体过度激活。本实验的目的是探究毒蕈碱型受体的选择性激活是否会诱导对AMPH的行为反应迟钝。为实现这一目的，雄性大鼠预先单次给予0.00、0.135、0.27或0.55 mg/kg的氧化震颤素（一种毒蕈碱激动剂），15天后用1.0 mg/kg剂量的AMPH进行激发。使用一套计算机化的活动计对大鼠注射前后的旷场行为进行测试。测试表明，在预先用氧化震颤素处理的动物中，对AMPH的行为反应，即自主活动增加，并未减弱，相反，还增强了。这种效应呈剂量依赖性，在给予0.55 mg/kg氧化震颤素的大鼠中最为明显。文中讨论了CVP和氧化震颤素效应差异的可能原因。
