title: Effects of adolescent treatment with nicotine, harmane, or norharmane in male Sprague-Dawley rats.
abstract: The initiation of tobacco use occurs most often in adolescence and may be especially detrimental as the adolescent brain is undergoing substantial development. In addition to nicotine, there are over 9000 other compounds present in tobacco products, including the β-carbolines harmane and norharmane. The present study aimed to determine the long-term effects of adolescent exposure to nicotine (NIC), harmane (HAR), or norharmane (NOR) on locomotor activity, learning and memory, anxiety-like behavior, motor coordination, and monoamine/metabolite concentrations in the striatum and nucleus accumbens of male Sprague-Dawley rats. Beginning on postnatal day (PND) 27 and continuing through PND 55, subjects received twice daily intraperitoneal injections of 1ml/kg saline (CON), 0.5mg NIC/kg, 0.5mg HAR/kg, or 0.5mg NOR/kg. Body weight, food, and water intake were measured daily (PNDs 27-96). Locomotor activity was assessed on PND 40 or 41, PND 55, and PNDs 81 and 82. Other behaviors (anxiety-like behavior, motor coordination, and spatial learning and memory) were assessed at least 25 days after drug exposure ended (PNDs 80-91). On PND 97, subjects were decapitated and the striatum and nucleus accumbens were dissected and frozen for analysis. NIC treatment significantly decreased food intake, but did not alter locomotor activity during or after treatment. HAR and NOR treatment, however, caused significant open field hypoactivity. Motor coordination, water maze performance, and concentrations of monoamines and metabolites in the striatum and nucleus accumbens were unaltered by any drug treatment. These results indicate a long-lasting effect on activity levels from adolescent HAR or NOR treatment; however, there were few long-lasting NIC effects. Given the paucity of data describing effects of HAR or NOR exposure, these data should encourage additional studies of these tobacco constituents as well as constituent combination studies.
authors.affiliation: Division of Neurotoxicology, National Center for Toxicological Research, U.S. Food & Drug Administration, Jefferson, AR 72079, United States.
authors.forename: Amy K
authors.initials: AK
authors.lastname: Goodwin
authors.affiliation: Division of Neurotoxicology, National Center for Toxicological Research, U.S. Food & Drug Administration, Jefferson, AR 72079, United States.
authors.forename: Susan M
authors.initials: SM
authors.lastname: Lantz-McPeak
authors.affiliation: Toxicologic Pathology Associates, Inc., Jefferson, AR 72079, United States.
authors.forename: Bonnie L
authors.initials: BL
authors.lastname: Robinson
authors.affiliation: Division of Neurotoxicology, National Center for Toxicological Research, U.S. Food & Drug Administration, Jefferson, AR 72079, United States.
authors.forename: C Delbert
authors.initials: CD
authors.lastname: Law
authors.affiliation: Division of Neurotoxicology, National Center for Toxicological Research, U.S. Food & Drug Administration, Jefferson, AR 72079, United States.
authors.forename: Syed F
authors.initials: SF
authors.lastname: Ali
authors.affiliation: Division of Neurotoxicology, National Center for Toxicological Research, U.S. Food & Drug Administration, Jefferson, AR 72079, United States. Electronic address: Sherry.Ferguson@FDA.HHS.GOV.
authors.forename: Sherry A
authors.initials: SA
authors.lastname: Ferguson
mesh_terms: D000367:Age Factors; D000818:Animals; D000831:Animals, Newborn; D001007:Anxiety / Q000139:chemically induced; D015306:Biogenic Monoamines / Q000378:metabolism; D001835:Body Weight / Q000187:drug effects; D002243:Carbolines; D003342:Corpus Striatum / Q000187:drug effects; D004326:Drinking / Q000187:drug effects; D004435:Eating / Q000187:drug effects; D005106:Exploratory Behavior / Q000187:drug effects; D006247:Harmine / Q000031:analogs & derivatives* / Q000494:pharmacology; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D009043:Motor Activity / Q000187:drug effects; D009069:Movement Disorders / Q000209:etiology*; D009498:Neurotoxins / Q000494:pharmacology*; D009538:Nicotine / Q000494:pharmacology*; D018722:Nicotinic Agonists / Q000494:pharmacology*; D009714:Nucleus Accumbens / Q000187:drug effects; D011597:Psychomotor Performance / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D015306:Biogenic Monoamines; D002243:Carbolines; D009498:Neurotoxins; D018722:Nicotinic Agonists; D006247:Harmine; D009538:Nicotine; C005010:harman; C010262:norharman
keywords: Adolescence; Behavior; Harmane; Nicotine; Norharmane; Rat