Bhakthavatsalam P, Kamatchi G L, Ghosh M N
Life Sci. 1985 Aug 19;37(7):635-43. doi: 10.1016/0024-3205(85)90430-8.
Tolerance to the anorexic effect of d-amphetamine was studied in rats with selective dopamine lesions in the forebrain by means of 6-hydroxy dopamine, and measuring the food intake during two consecutive 2 h periods. Lesions placed in the perifornical hypothalamus (PFH) strongly antagonised the anorexic effect, whereas, lesions produced via intraventricular injections affected the anorexia only marginally. Amphetamine anorexia observed in the first 2 h in control and lesioned groups remained persistently, without any evidence of tolerance, up to 2 weeks of treatment. The second 2 h food intake exhibited a progressive increase which contributed to the apparent tolerance seen in total 4 h food intake in the control and lesioned animals. The onset and completion of this apparent tolerance was markedly delayed in the dopamine depleted group; lesions placed in the relatively medial areas delayed the tolerance development more effectively than that of PFH lesions. The stimulant effect of amphetamine on locomotion was abolished in lesioned animals. The results indicate that an apparent tolerance to amphetamine anorexia still developed in animals with forebrain dopamine loss. Although both the beta adrenergic and dopaminergic systems act together in mediating AMPH anorexia, the onset and the rate of completion of tolerance appear to be under the influence of hypothalamic dopaminergic system.
通过6-羟基多巴胺在前脑制造选择性多巴胺损伤的大鼠中，研究了对d-苯丙胺厌食作用的耐受性，并在连续两个2小时时间段内测量食物摄入量。位于穹窿周下丘脑（PFH）的损伤强烈拮抗厌食作用，而通过脑室内注射产生的损伤对厌食的影响仅微乎其微。在对照组和损伤组中，在最初2小时观察到的苯丙胺厌食在长达2周的治疗期间持续存在，没有任何耐受性的证据。第二个2小时的食物摄入量逐渐增加，这导致了对照组和损伤动物在总共4小时食物摄入量中出现明显的耐受性。多巴胺耗竭组中这种明显耐受性的开始和完成明显延迟；位于相对内侧区域的损伤比PFH损伤更有效地延迟了耐受性的发展。损伤动物中苯丙胺对运动的刺激作用被消除。结果表明，在前脑多巴胺缺失的动物中，对苯丙胺厌食仍会出现明显的耐受性。尽管β-肾上腺素能和多巴胺能系统在介导AMPH厌食中共同起作用，但耐受性的开始和完成速度似乎受下丘脑多巴胺能系统的影响。
