title: Common effects of fat, ethanol, and nicotine on enkephalin in discrete areas of the brain.
abstract: Fat, ethanol, and nicotine share a number of properties, including their ability to reinforce behavior and produce overconsumption. To test whether these substances act similarly on the same neuronal populations in specific brain areas mediating these behaviors, we administered the substances short-term, using the same methods and within the same experiment, and measured their effects, in areas of the hypothalamus (HYPO), amygdala (AMYG), and nucleus accumbens (NAc), on mRNA levels of the opioid peptide, enkephalin (ENK), using in situ hybridization and on c-Fos immunoreactivity (ir) to indicate neuronal activity, using immunofluorescence histochemistry. In addition, we examined for comparison another reinforcing substance, sucrose, and also took measurements of stress-related behaviors and circulating corticosterone (CORT) and triglycerides (TG), to determine if they contribute to these substances' behavioral and physiological effects. Adult Sprague-Dawley rats were gavaged three times daily over 5 days with 3.5 mL of water, Intralipid (20% v/v), ethanol (12% v/v), nicotine (0.01% w/v) or sucrose (22% w/v) (approximately 7 kcal/dose), and tail vein blood was collected for measurements of circulating CORT and TG. On day five, animals were sacrificed, brains removed, and the HYPO, AMYG, and NAc processed for single- or double-labeling of ENK mRNA and c-Fos-ir. Fat, ethanol, and nicotine, but not sucrose, increased the single- and double-labeling of ENK and c-Fos-ir in precisely the same brain areas, the middle parvocellular but not lateral area of the paraventricular nucleus, central but not basolateral nucleus of the AMYG, and core but not shell of the NAc. While having little effect on stress-related behaviors or CORT levels, fat, ethanol, and nicotine all increased circulating levels of TG. These findings suggest that the overconsumption of these three substances and their potential for abuse are mediated by the same populations of ENK-expressing neurons in specific nuclei of the hypothalamus and limbic system.
authors.affiliation: Laboratory of Behavioral Neurobiology, The Rockefeller University, New York, NY, USA.
authors.forename: G-Q
authors.initials: GQ
authors.lastname: Chang
authors.affiliation: Laboratory of Behavioral Neurobiology, The Rockefeller University, New York, NY, USA.
authors.forename: O
authors.initials: O
authors.lastname: Karatayev
authors.affiliation: Laboratory of Behavioral Neurobiology, The Rockefeller University, New York, NY, USA.
authors.forename: J R
authors.initials: JR
authors.lastname: Barson
authors.affiliation: Laboratory of Behavioral Neurobiology, The Rockefeller University, New York, NY, USA.
authors.forename: S C
authors.initials: SC
authors.lastname: Liang
authors.affiliation: Laboratory of Behavioral Neurobiology, The Rockefeller University, New York, NY, USA. Electronic address: leibow@rockefeller.edu.
authors.forename: S F
authors.initials: SF
authors.lastname: Leibowitz
mesh_terms: D000818:Animals; D001921:Brain / Q000187:drug effects* / Q000378:metabolism*; D002492:Central Nervous System Depressants / Q000494:pharmacology; D003345:Corticosterone / Q000097:blood; D019422:Dietary Sucrose / Q000008:administration & dosage; D004655:Emulsions / Q000008:administration & dosage; D004745:Enkephalins / Q000378:metabolism*; D000431:Ethanol / Q000494:pharmacology; D005217:Fat Emulsions, Intravenous / Q000008:administration & dosage; D005455:Fluorescent Antibody Technique; D017403:In Situ Hybridization; D008297:Male; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism*; D009538:Nicotine / Q000494:pharmacology; D018722:Nicotinic Agonists / Q000494:pharmacology; D010743:Phospholipids / Q000008:administration & dosage; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D017207:Rats, Sprague-Dawley; D013024:Soybean Oil / Q000008:administration & dosage; D014280:Triglycerides / Q000097:blood
chemical_list: D002492:Central Nervous System Depressants; D019422:Dietary Sucrose; D004655:Emulsions; D004745:Enkephalins; D005217:Fat Emulsions, Intravenous; D018722:Nicotinic Agonists; D010743:Phospholipids; D016760:Proto-Oncogene Proteins c-fos; D012333:RNA, Messenger; D014280:Triglycerides; C545823:soybean oil, phospholipid emulsion; D000431:Ethanol; D009538:Nicotine; D013024:Soybean Oil; D003345:Corticosterone
keywords: Amygdala; Hypothalamus; Nucleus accumbens; Rat; Sucrose
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