title: Nicotine and ethanol co-use in Long-Evans rats: Stimulatory effects of perinatal exposure to a fat-rich diet.
abstract: Clinical studies demonstrate frequent co-existence of nicotine and alcohol abuse and suggest that this may result, in part, from the ready access to and intake of fat-rich diets. Whereas animal studies show that high-fat diet intake in adults can enhance the consumption of either nicotine or ethanol and that maternal consumption of a fat-rich diet during pregnancy increases operant responding for nicotine in offspring, little is known about the impact of dietary fat on the co-abuse of these two drugs. The goal of this study was to test in Long-Evans rats the effects of perinatal exposure to fat on the co-use of nicotine and ethanol, using a novel paradigm that involves simultaneous intravenous (IV) self-administration of these two drugs. Fat- vs. chow-exposed offspring were characterized and compared, first in terms of their nicotine self-administration behavior, then in terms of their nicotine/ethanol self-administration behavior, and lastly in terms of their self-administration of ethanol in the absence of nicotine. The results demonstrate that maternal consumption of fat compared to low-fat chow during gestation and lactation significantly stimulates nicotine self-administration during fixed-ratio testing. It also increases nicotine/ethanol self-administration during fixed-ratio and dose-response testing, with BEC elevated to 120 mg/dL, and causes an increase in breakpoint during progressive ratio testing. Of particular note is the finding that rats perinatally exposed to fat self-administer significantly more of the nicotine/ethanol mixture as compared to nicotine alone, an effect not evident in the chow-control rats. After removal of nicotine from the nicotine/ethanol mixture, this difference between the fat- and chow-exposed rats was lost, with both groups failing to acquire the self-administration of ethanol alone. Together, these findings suggest that perinatal exposure to a fat-rich diet, in addition to stimulating self-administration of nicotine, causes an even greater vulnerability to the excessive co-use of nicotine and ethanol.
authors.affiliation: Laboratory of Behavioral Neurobiology, The Rockefeller University, 1230 York Avenue, New York, NY 10065, USA.
authors.forename: Olga
authors.initials: O
authors.lastname: Karatayev
authors.affiliation: Laboratory of Behavioral Neurobiology, The Rockefeller University, 1230 York Avenue, New York, NY 10065, USA.
authors.forename: Olga
authors.initials: O
authors.lastname: Lukatskaya
authors.affiliation: Laboratory of Behavioral Neurobiology, The Rockefeller University, 1230 York Avenue, New York, NY 10065, USA.
authors.forename: Sang-Ho
authors.initials: SH
authors.lastname: Moon
authors.affiliation: Laboratory of Behavioral Neurobiology, The Rockefeller University, 1230 York Avenue, New York, NY 10065, USA.
authors.forename: Wei-Ran
authors.initials: WR
authors.lastname: Guo
authors.affiliation: Laboratory of Behavioral Neurobiology, The Rockefeller University, 1230 York Avenue, New York, NY 10065, USA.
authors.forename: Dan
authors.initials: D
authors.lastname: Chen
authors.affiliation: Laboratory of Behavioral Neurobiology, The Rockefeller University, 1230 York Avenue, New York, NY 10065, USA.
authors.forename: Diane
authors.initials: D
authors.lastname: Algava
authors.affiliation: Laboratory of Behavioral Neurobiology, The Rockefeller University, 1230 York Avenue, New York, NY 10065, USA.
authors.forename: Susan
authors.initials: S
authors.lastname: Abedi
authors.affiliation: Laboratory of Behavioral Neurobiology, The Rockefeller University, 1230 York Avenue, New York, NY 10065, USA. Electronic address: leibow@rockefeller.edu.
authors.forename: Sarah F
authors.initials: SF
authors.lastname: Leibowitz
mesh_terms: D000818:Animals; D003216:Conditioning, Operant / Q000187:drug effects; D059305:Diet, High-Fat; D004041:Dietary Fats / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D000431:Ethanol / Q000008:administration & dosage* / Q000097:blood / Q000494:pharmacology*; D005260:Female; D008297:Male; D009538:Nicotine / Q000008:administration & dosage* / Q000494:pharmacology*; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000523:psychology*; D051381:Rats; D020318:Rats, Long-Evans; D012055:Reinforcement Schedule; D012646:Self Administration
chemical_list: D004041:Dietary Fats; D000431:Ethanol; D009538:Nicotine
keywords: Co-abuse; Gestation; Intravenous; Offspring; Operant responding; Self-administration