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Cocaine vaccines: Antibody protection against relapse in a rat model

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TLDR
It is suggested that immunopharmacotherapy may offer a promising means to treat cocaine abuse by aiding in the prevention of relapse and the ability of antibodies to block the reinforcing effects of the drug.
Abstract
The efficacy of active immunization with the cocaine immunogen GNC-keyhole limpet hemocyanin (KLH) in preventing cocaine self-administration reinstatement was assessed in rats. An animal model of relapse was used where rats were trained to self-administer cocaine, subjected to a period of extinction by substituting the drug for saline, vaccinated, and re-exposed to cocaine. Compared with controls, animals immunized with GNC-KLH did not reinstate cocaine self-administration behavior when given a noncontingent cocaine infusion on two consecutive days. Upon double and triple infusions, 38–62% of vaccinated animals failed to reinstate as compared with full reinstatement in all control animals. Exposure to ad libitum cocaine reinstated baseline values in control animals and resulted in double to triple the baseline values of self-infusions in vaccinated animals, suggesting a partial antibody-mediated blockade of cocaine access to the central nervous system. This compensating effect was blocked by passive immunization pretreatment with the monoclonal IgG GNC92H2 in both vaccinated and control groups. To further assess the surmountability potential of GNC-KLH-induced antibody titers by cocaine self-administration, and the capacity of these titers to block the reinforcing effects of the drug, rats were tested at various doses of cocaine (0.015–0.5 mg/infusion). Active immunization with GNC-KLH produced approximately an 8-fold rightward shift of the dose-effect function for cocaine. The results reported suggest that immunopharmacotherapy may offer a promising means to treat cocaine abuse by aiding in the prevention of relapse.

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Journal ArticleDOI

The reinstatement model of drug relapse: history, methodology and major findings.

TL;DR: The data derived from studies using the reinstatement model suggest that the neuronal events that mediate drug-, cue- and stress-induced reinstatement of drug seeking are not identical, and that the duration of the withdrawal period following cocaine and heroin self-administration has a profound effect on reinstatement induced by drug cues and stress.
Journal ArticleDOI

Neurobiology of Relapse to Heroin and Cocaine Seeking: A Review

TL;DR: The main conclusion of this review is that the neuronal mechanisms involved in relapse to heroin and cocaine seeking induced by drug priming, drug cues, and stressors are to a large degree dissociable.
Journal ArticleDOI

Vaccine pharmacotherapy for the treatment of cocaine dependence.

TL;DR: The conjugated cocaine vaccine was well tolerated and cocaine specific antibodies persisted at least six months and the likelihood of using cocaine decreased in subjects who received the more intense vaccination schedule.
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Immunotherapy for the treatment of drug abuse

TL;DR: Current immunotherapies already show efficacy, but improved antigen design and antibody engineering promise highly specific and rapidly developed treatments for both existing and future addictions.
Journal ArticleDOI

A second-generation vaccine protects against the psychoactive effects of cocaine

TL;DR: The results indicate that these immunopharmacotherapeutic agents have significant cocaine-blockade potential and therefore may offer an effective strategy for the treatment of cocaine abuse.
References
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Journal ArticleDOI

Derivation of specific antibody-producing tissue culture and tumor lines by cell fusion

TL;DR: Cell fusion techniques have been used to produce hybrids between myeloma cells and antibody‐producing cells that are permanently adapted to grow in tissue culture and are capable of inducing antibody-producing tumors in mice.
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Reinstatement of cocaine-reinforced responding in the rat

TL;DR: The final experiment showed that a tone that had been paired with drug infusions acquired a statistically significant tendency to facilitate responding when tested during extinction but this effect disappeared after the first test presentation of the tone.
Journal ArticleDOI

Medical complications of cocaine abuse.

TL;DR: The earliest known use of cocaine, as suggested by the finding of coca leaves in the tombs of Indian mummies, was in 600 A.D, but it was not until 1855 that cocaine was isolated from the leaves.
Journal ArticleDOI

Fusion between immunoglobulin-secreting and nonsecreting myeloma cell lines.

TL;DR: The defects in two nonsecreting variant clones of the mouse plasmacytoma MOPC 21 (P3) were studied by tissue culture methods and the variants (NSI and NSIII) do not synthesize detectable heavy chains.
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