2-Mercaptoacetate and 2-deoxy-D-glucose induce Fos-like immunoreactivity in rat brain.
2-Deoxy-D-glucose (2-DG) and 2-mercaptoacetate (MA) are antimetabolic drugs that selectively antagonize glucose and fatty acid utilization, respectively, and stimulate feeding. Fos immunohistochemistry was employed to identify brain neurons activated by these drugs and to assess the role of the vagus nerve in the drug effects. Remote intravenous infusions of both MA and 2-DG induced Fos-like immunoreactivity (Fos-li) in specific brain sites, but the pattern was different for the two drugs. Mercaptoacetate induced Fos-li in the nucleus of the solitary tract (NTS), the central subnucleus of the lateral parabrachial nucleus (1PBN), the central nucleus of the amygdala (CNA, lateral part) and the dorsal motor nucleus of the vagus (DMV). Induction of Fos-li in the brain by MA was totally abolished by vagotomy. 2-Deoxy-D-glucose also induced Fos-li in the NTS, CNA (lateral part) and DMV, as well as in the external 1PBN subnucleus, locus coeruleus, paraventricular and supraoptic hypothalamic nuclei, and in scattered cells throughout the diencephalon. Induction of Fos-li by 2-DG was not blocked by vagotomy. Results suggest that 2-DG's effects on Fos-li are mediated by a direct central action, whereas MA's effects are mediated by peripheral sensory neurons. Thus, availability of glucose and fatty acids influences the activity of specific brain sites by different neural mechanisms. The correlation of Fos-immunoreactive sites with sites where lesions have been shown to cause deficits in MA- and 2-DG-induced feeding indicates that c-fos expression defines in part the central pathways involved in the metabolic control of feeding.(ABSTRACT TRUNCATED AT 250 WORDS)
Department of Veterinary and Comparative Anatomy, Physiology and Pharmacology, Washington State University, Pullman 99164-6520.
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D000818:Animals; D001923:Brain Chemistry / Q000187:drug effects*; D003847:Deoxyglucose / Q000494:pharmacology*; D007150:Immunohistochemistry; D008297:Male; D016760:Proto-Oncogene Proteins c-fos / Q000032:analysis / Q000187:drug effects*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013864:Thioglycolates / Q000494:pharmacology*; D014630:Vagus Nerve / Q000502:physiology
D016760:Proto-Oncogene Proteins c-fos; D013864:Thioglycolates; C017487:2-mercaptoacetate; D003847:Deoxyglucose