Immunization to nicotine with a peptide-based vaccine composed of a conformationally biased agonist of C5a as a molecular adjuvant

Sanderson, Sam D.; Cheruku, Srinivasa R.; Padmanilayam, Maniyan P.; Vennerstrom, Jonathan L.; Thiele, Geoffrey M.; Palmatier, Matthew I.; Bevins, Rick A.

doi:10.1016/s1567-5769(02)00260-6

Cited by 63 publications

(52 citation statements)

References 24 publications

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“…This training resulted in a drug state-specific goal-tracking CR. These studies extend our previous findings with nicotine Sanderson et al, 2003) to other drug states (amphetamine and CDP) and to an auditory CS (white noise). Importantly, we also found that the CR was pharmacologically specific; changes in the salience (ie dose) and pharmacological properties (ie compound) of the drugs decreased CS-specific goal tracking.…”

Section: Discussionsupporting

confidence: 88%

“…The finding that a drug state-specific CR was controlled by amphetamine extends our previous research with nicotine Sanderson et al, 2003) to another psychomotor stimulant that has some distinct pharmacological actions in the central nervous system . This generality is further extended by the finding that the anxiolytic CDP readily serves as a drug feature that signals a CS-US association.…”

Section: Discussionsupporting

confidence: 82%

“…Recent experiments from our laboratory have also used drug states to set the occasion for pairings between stimuli Sanderson et al, 2003). In that research, we used nicotine (0.4 mg/kg) to signal when a light cue (conditional stimulus or CS) would be followed by brief access to sucrose (unconditional stimulus or US).…”

Section: Introductionmentioning

confidence: 99%

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Stimulus Properties of Nicotine, Amphetamine, and Chlordiazepoxide as Positive Features in a Pavlovian Appetitive Discrimination Task in Rats

Palmatier

Wilkinson

Metschke

et al. 2004

Neuropsychopharmacol

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Recent experiments from our laboratory have demonstrated that drug states can signal when environmental cues will be followed by rewarding outcomes (ie Pavlovian conditioning). However, little is known about the generality of this approach and whether it can be used for studying the pharmacological properties of drug states. Accordingly, the present experiments tested the pharmacological specificity of nicotine (0.4 mg/kg), amphetamine (1 mg/kg), and chlordiazepoxide (CDP, 5 mg/kg) in this Pavlovian drug discrimination procedure. Following drug administration, presentation of a conditional stimulus (CS) was followed by brief access to sucrose. When saline was administered, the same CS was presented but sucrose was withheld. In substitution tests, rats in each condition received varying doses of all training drugs and caffeine. Anticipatory food seeking developed during the CS on drug sessions but not on saline sessions for all drug features (ie drug state-specific conditional response (CR)). In generalization tests, this CR decreased as a function of decreases in the training dose. Median effective doses (ED 50 s) were calculated for nicotine (0.054 mg/kg), amphetamine (0.26 mg/kg), and CDP (2.48 mg/kg). No compound tested substituted for the CDP training drug. Partial substitution was evident between nicotine and amphetamine; CDP did not substitute for either of these drug features. Caffeine fully substituted for nicotine (ED 50 ¼ 15.45 mg/kg) and amphetamine (ED 50 ¼ 3.70 mg/kg), but not for CDP. These results are consistent with the hypothesis that drug states can occasion appetitive Pavlovian CRs in a pharmacologically specific manner.

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Section: Discussionsupporting

confidence: 88%

Section: Discussionsupporting

confidence: 82%

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Stimulus Properties of Nicotine, Amphetamine, and Chlordiazepoxide as Positive Features in a Pavlovian Appetitive Discrimination Task in Rats

Palmatier

Wilkinson

Metschke

et al. 2004

Neuropsychopharmacol

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“…The Sanders et al vaccine developed at the University of Nebraska uses a modified form of the complement compound C5a as its carrier compound. 15 The adjuvants used in the clinical trials are classical adjuvants such as alum hydroxide or phosphate. The information in the public domain as far as the adjuvants are concerned is not complete and the companies may evaluate proprietary adjuvant formulations in their trials.…”

Section: Vaccines Against Nicotine Under Evaluation In Clinical Trialsmentioning

confidence: 99%

Vaccines against nicotine

Cerný

Cerny²

2009

Human Vaccines

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“…We believe that much more programmatic and parametric research is needed on vaccine design, formulation, and immunization schedule, as well as their impact on nicotinespecific antibody production and any accompanying changes in the pharmacokinetic and pharmacodynamic effects of nicotine. This research will likely include how the nicotine hapten is spaced and/or oriented on the carrier protein, the optimal number of haptens per carrier protein, how the nicotine is conjugated to the carrier protein, alternates to carrier protein immunoconjugate designs such as the use of peptide-based molecular adjuvants [14], and how immunization variables such as number and spacing affect vaccine efficacy [6,7].…”

Section: Expert Opinionmentioning

confidence: 99%