Neurotoxic amino acid lesions of the lateral hypothalamus: a parametric comparison of the effects of ibotenate, N-methyl-D,L-aspartate and quisqualate in the rat.

Separate groups of rats received unilateral lesions of the lateral hypothalamus by one of the 3 amino-acid neurotoxins, ibotenic acid (IBO), N-methyl-D,L-aspartic acid (NMA) or quisqualic acid (QA). A parametric comparison was made between the toxins on the extent of neuronal cell loss and the specificity of damage, by a systematic variation of both the volume (0.25-1.0 mm3) and concentration (0.03-0.12 M) injected. Neurotoxic potency on hypothalamic neurones varied in the order IBO greater than NMA greater than QA. All 3 toxins spared magnocellular supraoptic and accessory nuclei as well as medial hypothalamic neurones. Extrahypothalamic damage differed between the toxins: ventral thalamic neurones were susceptible to NMA and QA but only slightly to IBO, whereas the medial amygdala was sensitive to IBO but not NMA or QA. All 3 toxins spared ascending monoamine systems passing through the lateral hypothalamus, as assessed by biochemical assays of forebrain dopamine and serotonin. However, IBO induced a bilateral increase in dopamine levels, which was interpreted as an indirect consequence of the loss of lateral hypothalamic efferents projecting to the midbrain.