Heffner T G, Zigmond M J, Stricker E M
J Pharmacol Exp Ther. 1977 May;201(2):386-99.
The effects on food intake of treatments which alter central dopaminergic function were examined in rats. Doses of d-amphetamine that increased the conversion of 3H-tyrosine to 3H-dopamine in the brain were found to decrease food intake, an effect that was reduced by the systemic administration of the dopaminergic antagonists alpha-methyltyrosine, haloperidol or spiroperidol. The dopaminergic agonists, apomorphine, dopa, cocaine and methylphenidated, also reduced feeding and these effects were attenuated by low doses of spiroperidol. In larger doses, spiroperidol itself decreased feeding, and this effect was potentiated by alpha-methyltyrosine. The ability of dopaminergic agonists and antagonists to inhibit food intake was also observed in rats treated with 6-hhyroxydopamine so as to produce a selective 83% depletion of dopamine. In these animals, d-amphetamine was found to be less effective as an anorexic agent, whereas dopa, apomorphine, alpha-methyltyrosine and spiroperidol each was more effective in reducing food intake. These alterations in sensitivity may reflect neurochemical changes which occur at residual dopaminergic synapses after subtotal lesions of dopaminergic neurons. We conclude that both increases and decreases in central dopaminergic activity can reduce feeding and propose that some intermediate rate of dopamine release provides an optimal level of neuronal activity for feeding by the hungry animal.
研究了改变中枢多巴胺能功能的处理对大鼠食物摄入量的影响。发现能增加脑中3H-酪氨酸向3H-多巴胺转化的右旋苯丙胺剂量会减少食物摄入量，多巴胺能拮抗剂α-甲基酪氨酸、氟哌啶醇或螺哌啶醇全身给药可减弱这种作用。多巴胺能激动剂阿扑吗啡、多巴、可卡因和哌醋甲酯也会减少进食，低剂量螺哌啶醇可减弱这些作用。大剂量时，螺哌啶醇本身会减少进食，α-甲基酪氨酸可增强这种作用。在用6-羟基多巴胺处理以导致多巴胺选择性耗竭83%的大鼠中，也观察到了多巴胺能激动剂和拮抗剂抑制食物摄入的能力。在这些动物中，发现右旋苯丙胺作为厌食剂的效果较差，而多巴、阿扑吗啡、α-甲基酪氨酸和螺哌啶醇在减少食物摄入方面都更有效。敏感性的这些改变可能反映了多巴胺能神经元部分损伤后残余多巴胺能突触处发生的神经化学变化。我们得出结论，中枢多巴胺能活性的增加和减少都可减少进食，并提出多巴胺释放的某种中间速率为饥饿动物的进食提供了最佳水平的神经元活动。
