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

M. H. Hastings, P. Winn, S. B. Dunnett

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Abstract

Separate groups of rats received unilateral lesions of the lateral hypothaamus 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 > NMA > QA. All 3 toxins spared magnocellular supraopic 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.
Original languageEnglish
Pages (from-to)248-256
Number of pages9
JournalBrain Research
Volume360
Issue number1-2
DOIs
Publication statusPublished - 23 Dec 1985

Keywords

  • ibotenic acid
  • lateral hypothalamus
  • N-methyl aspartic acid
  • quisqualic acid
  • animal experiment
  • central nervous system
  • drug comparison
  • neurotoxicity
  • rat
  • neurotoxic amino acid lesions

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