title: Effects of adolescent nicotine exposure and withdrawal on intravenous cocaine self-administration during adulthood in male C57BL/6J mice.
abstract: Studies of adolescent drug use show (1) a pattern in which the use of tobacco precedes the use of other drugs and (2) a positive relationship between adolescent tobacco use and later drug use. These observations have led to the hypothesis that a causal relationship exists between early exposure to nicotine and the later use of hard drugs such as cocaine. Using male C57BL/6J mice, we tested the hypothesis that nicotine exposure in adolescence leads to increased intravenous self-administration (IVSA) of cocaine in adulthood. Using miniature osmotic pumps, we exposed mice and their littermate controls to nicotine (24 mg/kg/day) or vehicle, respectively, over the entire course of adolescence [postnatal days (P) 28-56]. Nicotine exposure was terminated on P56 and mice were not exposed to nicotine again during the experiment. On P73, mice were allowed to acquire cocaine IVSA (1.0 mg/kg/infusion) and a dose-response curve was generated (0.18, 0.32, 0.56, 1.0, 1.8 mg/kg/infusion). Lever pressing during extinction conditions was also evaluated. All mice rapidly learned to lever press for the combination of cocaine infusions and non-drug stimuli. Analysis of the dose-response curve revealed that adolescent nicotine-exposed mice self-administered significantly more (P < 0.05) cocaine than controls at all but the highest dose. No significant differences were observed between adolescent nicotine-exposed and control mice during the acquisition or extinction stages. These results indicate that adolescent nicotine exposure can increase cocaine IVSA in mice, which suggests the possibility of a causal link between adolescent tobacco use and later cocaine use in humans.
authors.affiliation: Department of Psychology, University of Memphis, Memphis, TN, USA.
authors.forename: Price E
authors.initials: PE
authors.lastname: Dickson
authors.forename: Mellessa M
authors.initials: MM
authors.lastname: Miller
authors.forename: Tiffany D
authors.initials: TD
authors.lastname: Rogers
authors.forename: Charles D
authors.initials: CD
authors.lastname: Blaha
authors.forename: Guy
authors.initials: G
authors.lastname: Mittleman
mesh_terms: D000293:Adolescent; D000294:Adolescent Behavior / Q000187:drug effects; D017668:Age of Onset; D000704:Analysis of Variance; D000818:Animals; D001835:Body Weight / Q000187:drug effects; D002404:Catheterization; D003042:Cocaine / Q000008:administration & dosage*; D019970:Cocaine-Related Disorders / Q000453:epidemiology / Q000209:etiology; D003216:Conditioning, Operant / Q000187:drug effects; D003367:Cotinine / Q000097:blood; D004195:Disease Models, Animal; D018765:Dopamine Uptake Inhibitors / Q000008:administration & dosage*; D004305:Dose-Response Relationship, Drug; D058999:Drug-Seeking Behavior / Q000187:drug effects*; D005108:Extinction, Psychological / Q000187:drug effects; D006801:Humans; D015918:Infusion Pumps, Implantable; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL / Q000235:genetics; D009538:Nicotine / Q000008:administration & dosage / Q000494:pharmacology*; D011897:Random Allocation; D051381:Rats; D012646:Self Administration / Q000706:statistics & numerical data; D014029:Tobacco Use Disorder / Q000150:complications / Q000453:epidemiology
chemical_list: D018765:Dopamine Uptake Inhibitors; D009538:Nicotine; D003042:Cocaine; D003367:Cotinine