NIC<sub>6</sub>-TT Vaccine Reduces Nicotine-Seeking Behavior and Expression of Nicotine-Induced Locomotor Sensitization in Rats

<b>Introduction</b>: Various models of nicotine vaccines have been evaluated. In humans, antibody levels are low and variable. In this sense, it is necessary to improve or optimize the nicotine vaccines already evaluated. We reported the efficacy of the M<sub>6</sub>-TT vacci...

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Main Authors: Susana Barbosa Méndez, Alberto Salazar-Juárez
Format: Article
Language:English
Published: MDPI AG 2025-03-01
Series:Brain Sciences
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Online Access:https://www.mdpi.com/2076-3425/15/4/364
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author Susana Barbosa Méndez
Alberto Salazar-Juárez
author_facet Susana Barbosa Méndez
Alberto Salazar-Juárez
author_sort Susana Barbosa Méndez
collection DOAJ
description <b>Introduction</b>: Various models of nicotine vaccines have been evaluated. In humans, antibody levels are low and variable. In this sense, it is necessary to improve or optimize the nicotine vaccines already evaluated. We reported the efficacy of the M<sub>6</sub>-TT vaccine. Recently, we reported the efficacy of the COC-TT vaccine, which was developed from the M<sub>6</sub>-TT vaccine. Both vaccines generate high titers of antibodies and attenuate heroin- or cocaine-induced behavioral effects in rodents. <b>Aims and Methods</b>: The objective of this study was to determine whether the antibodies generated by a tetanus toxoid-conjugated nicotine vaccine (NIC<sub>6</sub>-TT) can produce anti-nicotine antibodies and decrease the nicotine-induced reinforcing and psychomotor effects. Male Wistar rats were immunized with the NIC<sub>6</sub>-TT. A solid-phase antibody-capture ELISA was used to monitor antibody titer responses after each booster dose in vaccinated animals. The study used nicotine self-administration and nicotine locomotor sensitization testing to evaluate the nicotine-reinforcing and psychomotor effects. <b>Results</b>: The NIC<sub>6</sub>-TT vaccine could generate high and sustained levels of anti-nicotine antibodies. The antibodies reduced the nicotine self-administration and expression of nicotine locomotor sensitization. <b>Conclusions</b>: These findings suggest that the NIC<sub>6</sub>-TT vaccine generates a robust immunogenic response capable of reducing the reinforcing and psychomotor effects of nicotine, which supports its possible future use in clinical trials for the treatment of smokers. <b>Implications</b>: Smoking is the second most used psychoactive substance in the world, which is associated with millions of preventable deaths. An effective treatment is required. Nicotine vaccines must generate high levels of anti-nicotine antibodies, but above all, the decay curve of the antibodies must be very slow, so that they can provide long-term protection and support long-term smoking abstinence. The NIC<sub>6</sub>-TT vaccine meets these properties.
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spelling doaj-art-dc9e90a497e04ebfbc89b1d99d07c8982025-08-20T02:17:20ZengMDPI AGBrain Sciences2076-34252025-03-0115436410.3390/brainsci15040364NIC<sub>6</sub>-TT Vaccine Reduces Nicotine-Seeking Behavior and Expression of Nicotine-Induced Locomotor Sensitization in RatsSusana Barbosa Méndez0Alberto Salazar-Juárez1Subdirección de Investigaciones Clínicas, Laboratorio de Neurofarmacología Conductual, Microcirugía y Terapéutica Experimental, Instituto Nacional de Psiquiatría, México DF 14370, MexicoSubdirección de Investigaciones Clínicas, Laboratorio de Neurofarmacología Conductual, Microcirugía y Terapéutica Experimental, Instituto Nacional de Psiquiatría, México DF 14370, Mexico<b>Introduction</b>: Various models of nicotine vaccines have been evaluated. In humans, antibody levels are low and variable. In this sense, it is necessary to improve or optimize the nicotine vaccines already evaluated. We reported the efficacy of the M<sub>6</sub>-TT vaccine. Recently, we reported the efficacy of the COC-TT vaccine, which was developed from the M<sub>6</sub>-TT vaccine. Both vaccines generate high titers of antibodies and attenuate heroin- or cocaine-induced behavioral effects in rodents. <b>Aims and Methods</b>: The objective of this study was to determine whether the antibodies generated by a tetanus toxoid-conjugated nicotine vaccine (NIC<sub>6</sub>-TT) can produce anti-nicotine antibodies and decrease the nicotine-induced reinforcing and psychomotor effects. Male Wistar rats were immunized with the NIC<sub>6</sub>-TT. A solid-phase antibody-capture ELISA was used to monitor antibody titer responses after each booster dose in vaccinated animals. The study used nicotine self-administration and nicotine locomotor sensitization testing to evaluate the nicotine-reinforcing and psychomotor effects. <b>Results</b>: The NIC<sub>6</sub>-TT vaccine could generate high and sustained levels of anti-nicotine antibodies. The antibodies reduced the nicotine self-administration and expression of nicotine locomotor sensitization. <b>Conclusions</b>: These findings suggest that the NIC<sub>6</sub>-TT vaccine generates a robust immunogenic response capable of reducing the reinforcing and psychomotor effects of nicotine, which supports its possible future use in clinical trials for the treatment of smokers. <b>Implications</b>: Smoking is the second most used psychoactive substance in the world, which is associated with millions of preventable deaths. An effective treatment is required. Nicotine vaccines must generate high levels of anti-nicotine antibodies, but above all, the decay curve of the antibodies must be very slow, so that they can provide long-term protection and support long-term smoking abstinence. The NIC<sub>6</sub>-TT vaccine meets these properties.https://www.mdpi.com/2076-3425/15/4/364active vaccinationnicotineantibodiesNIC<sub>6</sub>-TT vaccinenicotine self-administrationnicotine locomotor sensitization
spellingShingle Susana Barbosa Méndez
Alberto Salazar-Juárez
NIC<sub>6</sub>-TT Vaccine Reduces Nicotine-Seeking Behavior and Expression of Nicotine-Induced Locomotor Sensitization in Rats
Brain Sciences
active vaccination
nicotine
antibodies
NIC<sub>6</sub>-TT vaccine
nicotine self-administration
nicotine locomotor sensitization
title NIC<sub>6</sub>-TT Vaccine Reduces Nicotine-Seeking Behavior and Expression of Nicotine-Induced Locomotor Sensitization in Rats
title_full NIC<sub>6</sub>-TT Vaccine Reduces Nicotine-Seeking Behavior and Expression of Nicotine-Induced Locomotor Sensitization in Rats
title_fullStr NIC<sub>6</sub>-TT Vaccine Reduces Nicotine-Seeking Behavior and Expression of Nicotine-Induced Locomotor Sensitization in Rats
title_full_unstemmed NIC<sub>6</sub>-TT Vaccine Reduces Nicotine-Seeking Behavior and Expression of Nicotine-Induced Locomotor Sensitization in Rats
title_short NIC<sub>6</sub>-TT Vaccine Reduces Nicotine-Seeking Behavior and Expression of Nicotine-Induced Locomotor Sensitization in Rats
title_sort nic sub 6 sub tt vaccine reduces nicotine seeking behavior and expression of nicotine induced locomotor sensitization in rats
topic active vaccination
nicotine
antibodies
NIC<sub>6</sub>-TT vaccine
nicotine self-administration
nicotine locomotor sensitization
url https://www.mdpi.com/2076-3425/15/4/364
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AT albertosalazarjuarez nicsub6subttvaccinereducesnicotineseekingbehaviorandexpressionofnicotineinducedlocomotorsensitizationinrats