Bendotti C, Borsini F, Cotecchia S, De Blasi A, Mennini T, Samanin R
Arch Int Pharmacodyn Ther. 1982 Nov;260(1):36-49.
No tolerance to the anorectic activity of d-amphetamine was found in rats given two daily injections of 1.25 mg/kg for 28 days. Such rats also presented no changes in the number of binding sites for serotonin and catecholamines in various brain areas. A 28-day treatment with 10 mg/kg d-amphetamine twice daily caused a significant reduction in the number of binding sites for 3H-dihydroalprenolol (beta adrenergic receptor ligand) in hippocampus, and 3H-spiroperidol (dopamine receptor ligand) in striatum and nucleus accumbens. This treatment did not modify the anorectic effect of 1.25 mg/kg of amphetamine but it markedly reduced the motor hyperactivity induced by this treatment and completely blocked the stereotyped licking and biting induced by apomorphine. Amphetamine stereotypy was not significantly reduced but disappeared faster in chronically treated rats. The possible reasons for the different results (tolerance or sensitization) reported by various authors on changes in amphetamine's effects on motor behaviour during chronic treatment are discussed.
给大鼠每日注射两次1.25毫克/千克的右旋苯丙胺,持续28天,未发现其对右旋苯丙胺的厌食活性产生耐受性。这些大鼠在各个脑区中血清素和儿茶酚胺的结合位点数量也未出现变化。每日两次用10毫克/千克的右旋苯丙胺进行为期28天的治疗,导致海马体中3H-二氢阿普洛尔(β肾上腺素能受体配体)以及纹状体和伏隔核中3H-螺哌啶醇(多巴胺受体配体)的结合位点数量显著减少。这种治疗并未改变1.25毫克/千克苯丙胺的厌食效果,但显著降低了该治疗所诱导的运动亢进,并完全阻断了阿扑吗啡所诱导的刻板舔舐和啃咬行为。苯丙胺刻板行为虽未显著降低,但在长期治疗的大鼠中消失得更快。讨论了不同作者报道的关于慢性治疗期间苯丙胺对运动行为影响变化的不同结果(耐受性或敏化)的可能原因。