Nasif F J, Ramírez O A, Cuadra G R, Orsingher O A
Departamento de Farmacología, Facultad de Ciencias Químicas, Universidad Nacional de Córdoba, Argentina.
Life Sci. 2001 Oct 12;69(21):2551-9. doi: 10.1016/s0024-3205(01)01335-2.
The spontaneous activity of locus coeruleus (LC) noradrenergic neurons was assessed by single unit recording in adult recovered rats undernourished at perinatal age as compared with wellnourished animals. Locus coeruleus activity, measured by the firing rate of noradrenergic neurons and the number of spontaneously active cells/track was significantly higher in deprived rats than in controls. In addition, dose-response curves for the inhibitory LC activity of clonidine showed a shift to the right in deprived animals indicating a subsensitivity of alpha2-adrenergic autoreceptors. This fact suggests an alteration in the negative feedback mechanism mediated by somatodentritic alpha2 autoreceptors that modulate the activity of LC neurons, and may account for the behavioral alterations attributed to early undernutrition. Repeated desipramine (DMI) administration to deprived rats reduced LC activity to values comparable to controls, which were not affected after a similar treatment. These data extend to previous reports on long-lasting or permanent plastic changes in the CNS induced by early undernutrition, which may be reverted by pharmacological manipulations. In addition, these results support the hypothesis that alterations induced by early undernutrition are in the same direction as and resemble those described for patients with panic disorders. Furthermore, together with behavioral alterations and selective anxiolytic effect of DMI and other drugs with antipanic effects described in early malnourished rats, the present data support the proposal that perinatally deprived rats may be a useful model for screening drugs with potential antipanic activity.
通过对围产期营养不良的成年恢复大鼠进行单单位记录，评估蓝斑（LC）去甲肾上腺素能神经元的自发活动，并与营养良好的动物进行比较。通过去甲肾上腺素能神经元的放电频率和自发活动细胞/轨迹数量来衡量，LC活动在营养缺乏的大鼠中显著高于对照组。此外，可乐定对LC抑制活性的剂量反应曲线在营养缺乏的动物中向右移动，表明α2-肾上腺素能自受体存在敏感性降低。这一事实表明，由体树突状α2自受体介导的负反馈机制发生改变，该机制调节LC神经元的活动，这可能是早期营养不良所致行为改变的原因。对营养缺乏的大鼠反复给予地昔帕明（DMI）可使LC活动降低至与对照组相当的值，而对照组在接受类似治疗后不受影响。这些数据扩展了先前关于早期营养不良诱导中枢神经系统长期或永久性可塑性变化的报道，这些变化可能通过药物操作得以逆转。此外，这些结果支持以下假设：早期营养不良引起的改变与惊恐障碍患者所描述的改变方向相同且相似。此外，结合早期营养不良大鼠中描述的行为改变以及DMI和其他具有抗惊恐作用药物的选择性抗焦虑作用，目前的数据支持以下提议：围产期营养不良的大鼠可能是筛选具有潜在抗惊恐活性药物的有用模型。
