Hilakivi I, Rinne J, Marjamäki P
Department of Physiology, Institute of Biomedicine, Faculty of Medicine, University of Helsinki, Finland.
Pol J Pharmacol. 1999 Jul-Aug;51(4):311-6.
Desipramine, a monoamine uptake inhibiting antidepressant, was given once a day sc from the 6th to the 22nd postnatal days, which is during infancy and preweanling in ontogenesis, to rats and its effects on dorsal striatal dopamine D1 and D2 receptor binding in adolescence were examined. The rats were decapitated, their dorsal striata were dissected on approximately the 34th postnatal day, and the maximal densities (Bmax) and affinities (Kd) of dopamine D1 and D2 receptors were assayed using [3H] SCH 23390 and [3H] spiperone as ligands. Desipramine did not affect the densities or affinities of dopamine D1 or D2 receptor binding, and tended to increase the D1/D2 density ratio. The Bmax of dopamine D2 receptors was higher in male than in female rats (p<0.01), the D1/D2 Bmax ratio tended to be lower in male than in female rats (p<0.07), and the Kd for D1 receptors tended to be lower in male than in female rats (p<0.05). There was no interaction between treatment and gender. We conclude that desipramine given at infancy and preweanling increases the susceptibility of adolescent rats to behavioral effects of dopamine agonists with an optimal, and relatively high SCH 23390/spiperone binding site density ratio. Furthermore, gender differences in dorsal striatal spiperone binding site densities, SCH 23390/spiperone density ratio, and SCH 23390 affinities may render male rats more vulnerable than female rats to expression of excessive stereotyped behavior.
去甲丙咪嗪是一种单胺摄取抑制性抗抑郁药,在出生后第6天至第22天(此阶段处于个体发育的婴儿期和断奶前阶段)每天一次皮下注射给大鼠,然后检测其对青春期大鼠背侧纹状体多巴胺D1和D2受体结合的影响。在出生后约第34天,将大鼠断头,解剖其背侧纹状体,使用[3H] SCH 23390和[3H] 螺哌隆作为配体测定多巴胺D1和D2受体的最大密度(Bmax)和亲和力(Kd)。去甲丙咪嗪不影响多巴胺D1或D2受体结合的密度或亲和力,且有增加D1/D2密度比的趋势。多巴胺D2受体的Bmax在雄性大鼠中高于雌性大鼠(p<0.01),D1/D2 Bmax比值在雄性大鼠中趋于低于雌性大鼠(p<0.07),D1受体的Kd在雄性大鼠中趋于低于雌性大鼠(p<0.05)。处理与性别之间没有相互作用。我们得出结论,在婴儿期和断奶前给予去甲丙咪嗪会增加青春期大鼠对多巴胺激动剂行为效应的易感性,此时具有最佳且相对较高的SCH 23390/螺哌隆结合位点密度比。此外,背侧纹状体螺哌隆结合位点密度、SCH 23390/螺哌隆密度比和SCH 23390亲和力的性别差异可能使雄性大鼠比雌性大鼠更容易表现出过度的刻板行为。