Vaccination against nicotine alters the distribution of nicotine delivered via cigarette smoke inhalation to rats

Abstract

Preclinical models of nicotine vaccine pharmacology have relied on i.v. or s.c. administration of nicotine. Models using cigarette smoke inhalation might more accurately simulate nicotine exposure in smokers. Nicotine vaccine effects were examined in rats using two cigarette smoke exposure models: a 10 minute nose-only exposure (NSE) producing serum nicotine levels equivalent to the nicotine boost from 1 cigarette in a smoker, and a two hour whole-body exposure (WBE) producing serum nicotine levels similar to those associated with regular midday smoking. Vaccination prior to 10 min smoke NSE reduced nicotine distribution to brain by 90%, comparable to its effect on nicotine administered i.v. Vaccination prior to 2 hr smoke WBE reduced nicotine distribution to brain by 35%. The nicotine concentration in broncheoalveolar lavage (BAL) fluid obtained after 2 hr WBE was increased by 230% in vaccinated rats but was also increased in rats passively immunized with a nicotine-specific monoclonal antibody, and so was likely due to transfer of antibody from serum rather than local production at the pulmonary mucosa. Nicotine-specific IgA was not detectable in BAL fluid, but titers in serum were appreciable at 21–25% of the IgG titer and could contribute to vaccine efficacy. Both vaccination and passive immunization are effective in reducing nicotine distribution to brain in rats when nicotine is delivered via inhaled cigarette smoke. These data validate results previously obtained in rodents for nicotine vaccines using i.v. or s.c. nicotine dosing and provide a quantitative method for studying aspects of nicotine exposure which are unique to cigarette smoke inhalation.

An Oxycodone Conjugate Vaccine Elicits Drug-Specific Antibodies that Reduce Oxycodone Distribution to Brain and Hot-Plate Analgesia

“…The primary action of addiction vaccines is presumed to be the binding of drug to antibody in serum, reducing the unbound or free drug concentration and its subsequent distribution to brain (Keyler et al, 2005;Pravetoni et al, 2011). Changes in OXY protein binding and the unbound concentration of OXY in serum after vaccination with OXY(Gly) 4 -KLH were substantial and strongly support this mechanism of action.…”

“…Male Holtzman rats weighing 350 g (Harlan Teklad, Madison, WI) were housed with a 12-h standard light/dark cycle. In immunogenicity, distribution, and behavioral studies, conjugates were injected intraperitoneally in a volume of 0.4 ml, at doses of 25 to 100 g by using complete Freund's adjuvant for the first injection and incomplete Freund's adjuvant for two subsequent booster injections at 3 and 6 weeks (Pravetoni et al, 2011). A total of three vaccinations were administered, at 0, 21, and 42 days.…”

Selective Effects of a Morphine Conjugate Vaccine on Heroin and Metabolite Distribution and Heroin-Induced Behaviors in Rats

“…Rats were immunized with M-KLH or unconjugated KLH at an immunogen dose of 25-100 mg. Immunogen was injected in a volume of 0.4 ml using either Freund's adjuvant i.p. or 2.5 mg/ml alum s.c. (Alhydrogel; Brenntag Biosector, Frederikssund, Denmark) (Pravetoni et al, 2011). Freund's complete adjuvant (EMD Millipore, Billerica, MA) was used for the first immunization while Freund's incomplete adjuvant (Sigma-Aldrich) was used for subsequent vaccine boosts.…”

Should We Embrace Vaccines for Treating Substance- Related Disorder, A Subset of Reward Deficiency Syndrome (RDS)?

“…In addition, antinicotine vaccines have been developed recently [16]. Antinicotine vaccines showed promise in animal models [17], however when administered to human smokers did not lead to changes in brain activity during smoking cue exposure [18].…”