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We previously showed different effects of tobacco and nicotine on fracture healing, but due to pump reservoir limits, maximum exposure period was 4 weeks. To allow flexibility in pre- and post-fracture exposure periods, the objective of this study was to compare a new oral administration route for nicotine to the established pump method. Four groups were studied: (1) pump saline, (2) pump saline + oral tobacco, (3) pump saline/nicotine + oral tobacco, and (4) pump saline + oral nicotine/tobacco. Sprague-Dawley rats (n = 84) received a transverse femoral fracture stabilized with an intramedullary pin 1 week after initiating dosing. After 3 weeks, no difference was found in torsional strength or stiffness between oral nicotine/tobacco or pump nicotine + tobacco, while energy absorption with oral nicotine/tobacco was greater than pump nicotine + tobacco ( p < 0.05). Compared to saline control, strength for oral nicotine/tobacco was higher than control ( p < 0.05), and stiffnesses for pump nicotine + tobacco and oral nicotine/tobacco were higher than control ( p < 0.05). No differences in energy were found for either nicotine-tobacco group compared to saline control. Mean serum cotinine (stable nicotine metabolite) was different between pump and oral nicotine at 1 and 4 weeks, but all groups were in the range of 1-2 pack/day smokers. In summary, relevant serum cotinine levels can be reached in rats with oral nicotine, and, in the presence of tobacco, nicotine can influence mechanical aspects of fracture healing, dependent on administration method. Caution should be exercised when comparing results of fracture healing studies using different methods of nicotine administration. © 2010 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 28:1235-1239, 2010 [ABSTRACT FROM AUTHOR]

The article discusses research on the physiological and behavioral effects of a nicotine conjugate vaccine on the acquisition and maintenance of nicotine self-administration in rats. It provides information on the methods and materials used in the study. It also discusses the results of the study.

Abstract: Degradation of heroin to 6-monoacetylmorphine (6-MAM) and then morphine happens rapidly in vivo and in vitro. The rates of heroin and 6-MAM degradation depend on the type of biological samples, and the duration and conditions of storage. In order to optimize conditions for measuring heroin and its metabolites in samples collected for pharmacokinetic studies in rats, we investigated the time course of degradation of heroin, 6-MAM, and morphine in four biological matrices: rat blood, rat brain homogenate, bovine serum, and human plasma under various conditions. Analyte concentrations were measured by LC–MS. The goal was to identify conditions that allow maximum flexibility in scheduling sample collection and analysis, as well as gain more information on the stability of heroin in blood and tissue samples. A solid-phase extraction method with ice-cold solvents, sodium fluoride (NaF) and a low pH (3.0) maintained sample stability. Quality controls were within 94.0–105% of the target value. Variability was 4.0–8.9% for all analytes within the range of 5–200ng/mL for heroin, 5–1000ng/mL for 6-MAM, and 10–200ng/mL for morphine. Heroin degradation to 6-MAM was faster in rat whole blood than in plasma, and faster in rat plasma than in rat brain homogenate. Maintaining NaF at 4mg/mL throughout processing enhanced stability; higher NaF concentrations added to whole blood caused hemolysis. Samples processed through solid phase extraction and stored as dried pellets at 80°C constituted the most stable environment for heroin, and was superior to the storing of samples in solution prior to or after extraction. Nevertheless, post-extraction heroin and 6-MAM levels declined by 6.7–8.3% over one week in rat plasma under these conditions, and by <1–4.7% in bovine serum or human plasma. [Copyright &y& Elsevier]

Abstract: Animal models of tobacco dependence typically rely on parenteral administration of pure nicotine. Models using cigarette smoke inhalation might more accurately simulate nicotine exposure in smokers. The primary goal of this study was to validate methods for administering cigarette smoke to rats using exposure conditions that were clinically relevant and also produced brain nicotine levels similar to those produced by behaviorally active doses of pure nicotine. A secondary goal was to begin examining the behavioral effects of smoke. Nose-only exposure (NOE) to smoke for 10–45min or whole-body exposure (WBE) to smoke for 1–4h produced serum nicotine concentrations similar to those in smokers (14–55ng/ml), without excessive carbon monoxide exposure. Daily nicotine (0.1mg/kg, s.c.) induced locomotor sensitization whereas 45-min NOE producing brain nicotine levels within the same range did not. Nicotine 0.125mg/kg s.c. reversed withdrawal from a chronic nicotine infusion as measured by elevations in intracranial self-stimulation thresholds whereas 4-h WBE producing similar brain nicotine levels did not. These data demonstrate the feasibility of delivering cigarette smoke to rats at clinically relevant doses, and provide preliminary evidence that the behavioral effects of nicotine delivered in smoke may differ from those of pure nicotine. [Copyright &y& Elsevier]

Abstract: Vaccination against nicotine is under investigation as a treatment for tobacco dependence. Passive immunization with nicotine-specific antibodies represents a complementary strategy to vaccination. A potential adverse effect of passive immunization in nicotine-dependent individuals is that it may lead to a rapid reduction in brain nicotine levels and trigger withdrawal. The goal of this study was to determine if passive immunization with the nicotine-specific monoclonal antibody Nic311 precipitated withdrawal in nicotine-dependent rats as measured by increases in brain reward thresholds and somatic signs. Another cohort of rats was used to measure brain nicotine levels after Nic311 administration. Nic311 30, 80 or 240 mg/kg reduced brain nicotine concentrations by 45, 83 or 92% compared to controls. None of these Nic311 doses precipitated withdrawal measured at intervals up to 72 h following antibody administration. Administration of the nicotinic antagonist mecamylamine precipitated a robust nicotine withdrawal syndrome. Therefore, a substantial, but not complete, acute reduction in brain nicotine levels following passive immunization was not sufficient to precipitate nicotine withdrawal in nicotine-dependent rats. The Nic311 doses used have been shown to attenuate the behavioral effects of nicotine, suggesting that the use of passive immunization to treat nicotine addiction is not likely to precipitate withdrawal. [Copyright &y& Elsevier]