De Montis M G, Gambarana C, Meloni D, Taddei I, Tagliamonte A
Institute of Pharmacology, University of Siena, Italy.
Brain Res. 1993 Mar 19;606(1):63-7. doi: 10.1016/0006-8993(93)91570-i.
Long-term exposure to different antidepressant treatments induces increased motor response to central stimulants, due to a selective supersensitivity of dopamine D2 receptors in the limbic areas. Such an effect is accompanied by down-regulation of dopamine D1 receptor number, and by a decreased response of adenylyl cyclase to dopamine stimulation in the limbic system. Moreover, the number of beta-adrenergic receptors and the response of adenylyl cyclase to beta-adrenergic stimulation in the cortex result to be reduced. The present data confirms that imipramine (10 mg/kg twice a day for 3 weeks) produces such effects, and shows that the co-administration of imipramine with MK-801 (administered by a subcutaneously implanted osmotic minipump delivering 0.05 mg/kg/day of the compound) prevented the occurrence of both the behavioral supersensitivity to quinpirole, and the decrease of dopamine D1 and beta-adrenergic receptor function.
长期接触不同的抗抑郁治疗会导致对中枢兴奋剂的运动反应增加，这是由于边缘区域多巴胺D2受体的选择性超敏反应。这种效应伴随着多巴胺D1受体数量的下调，以及边缘系统中腺苷酸环化酶对多巴胺刺激的反应降低。此外，皮质中β-肾上腺素能受体的数量以及腺苷酸环化酶对β-肾上腺素能刺激的反应也会降低。目前的数据证实，丙咪嗪（每天两次，每次10 mg/kg，持续3周）会产生这种效应，并表明丙咪嗪与MK-801联合使用（通过皮下植入的渗透微型泵给药，每天输送0.05 mg/kg的该化合物）可防止对喹吡罗的行为超敏反应以及多巴胺D1和β-肾上腺素能受体功能的降低。
