Up-regulation of neuropeptide Y receptors in the hypothalamus of monosodium glutamate-lesioned Sprague-Dawley rats

Monosodium-glutamate (MSG) is neurotoxic for brain regions devoid of blood-brain barrier when it is injected at high doses during the neonatal period. Neuropeptide Y (NPY) neurons in the arcuate nucleus are particularly sensitive to MSG treatment. But, despite of the large decrease of this potent orexigenic peptide, feeding behavior is only slightly affected. We hypothesized that the hypothalamic NPY receptor system might be modified in these rats. The present study characterizes hypothalamic NPY and NPY receptors in normal and MSG-treated rats. MSG-treated rats were lighter (p < 0.01) and ate 17% less than the control rats (p < 0.01). NPY levels in the mediobasal and mediodorsal hypothalamus were reduced in MSG-treated rats compared to normal rats (-26% and -43%, p < 0.05 and p < 0.01, respectively). Combined hypothalamic Y1 and Y5 NPY receptor density was increased in MSG-treated rats compared to normal rats (+25%, p < 0.04), but affinity remained unaltered. Blockade with a selective Y1 antagonist showed that the Y1 receptor subtype represented more than 90% of the combined Y1 and Y5 receptor populations. The up-regulation of the NPY receptors is an element necessary to maintain food intake at a sufficient level to allow survival and growth of the lesioned rats.