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.
D000818:Animals; D001224:Aspartic Acid / Q000031:analogs & derivatives* / Q000494:pharmacology; D004298:Dopamine / Q000032:analysis; D007026:Hypothalamic Area, Lateral / Q000187:drug effects*; D007051:Ibotenic Acid / Q000494:pharmacology*; D008297:Male; D008636:Mesencephalon / Q000187:drug effects; D016202:N-Methylaspartate; D009434:Neural Pathways / Q000187:drug effects; D010069:Oxadiazoles / Q000494:pharmacology*; D010080:Oxazoles / Q000494:pharmacology*; D016318:Quisqualic Acid; D051381:Rats; D011919:Rats, Inbred Strains; D012701:Serotonin / Q000032:analysis
D010069:Oxadiazoles; D010080:Oxazoles; D007051:Ibotenic Acid; D001224:Aspartic Acid; D012701:Serotonin; D016202:N-Methylaspartate; D016318:Quisqualic Acid; D004298:Dopamine