IntroductionThe classic pharmacopoeia used to attenuate cocaine dependence has proved a poor therapeutic efficacy. Based on this discouraging clinical and therapeutic panorama, since more than a decade, various researchers have developed new therapeutic strategies against cocaine addiction. These new experimental strategies are based on the structural design and synthesis of therapeutic vaccine formulations against cocaine addiction. ObjectiveTo describe the development and therapeutic evaluation of active immunization against cocaine. MethodA bibliographical search was made using PubMed, using as descriptors the words "Cocaine" and "Vaccine." 155 articles were obtained which were used for these review 46 items. ResultsAt preclinical level, active vaccination generates high levels of antibodies capable of recognizing with high specificity the cocaine present in the bloodstream, which attenuates the behavioral changes induced by different doses of cocaine. Discussion and conclusionPreclinical and clinical results have reinforced "proof of concept" active therapeutic vaccination to pharmacological control to cocaine use relapse in humans, but gave guidelines to the postulation and justification of synthesizing new models of anti-cocaine vaccines for human use.This experimental pharmacological strategy of "immunoprotective" nature has proven an effective treatment that significantly reduces drug-seeking behaviors, both at pre-clinical levels in the rodent model as well as in humans.Key words: Addiction, cocaine, active immune-protection, antibodies and pharmacotherapies. RESUMEN IntroducciónLa farmacopea clásica, empleada para atenuar la dependencia a ciertas drogas de abuso ilegal, como la cocaína, ha demostrado una pobre eficacia terapéutica. Basado en este desalentador panorama clínico-terapéutico, desde hace más de una década diversos investigadores han desarrollado nuevas estrategias terapéuticas contra la adicción a la cocaína. Estas nuevas estrategias experimentales están basadas en el diseño y la síntesis de formulaciones estructurales de vacunas terapéuticas contra la adicción a la cocaína. ObjetivoRealizar una descripción del desarrollo y la validación terapéutica de la inmunización activa contra la cocaína. MétodoSe realizó una búsqueda bibliográfica con el uso del PubMed, usando como descriptores las palabras "Cocaine" y "Vaccine". Se obtuvieron 155 artículos, de los cuales se usaron 46 para esta revisión. ResultadosA nivel preclínico, la vacunación activa genera altos niveles de anticuerpos capaces de reconocer con alta especificidad a la cocaína dentro del torrente sanguíneo, atenuando las alteraciones conductuales inducidas por diversas dosis de cocaína. Discusión y conclusiónLos resultados preclínicos y clínicos han reforzado "la prueba de concepto" terapéutica de la vacunación activa para el control farmacoló-gico de la recaída al consumo adictivo de la cocaína en el humano, sin embargo, dieron pauta a la postulación y a la justificación de sintetizar nuevos modelos de uso humano de vacuna...

Background: Anxiety and depression, key symptoms of the cocaine withdrawal syndrome in human addicts, are considered the main factors that precipitate relapse in chronic cocaine addiction. Preclinical studies have found that rodents exposed to different withdrawal periods show an increase in anxiety and depressive-like behavior. Mirtazapine – a tetracyclic medication – is used primarily to treat depression and, sometimes, anxiety. It has also successfully improved withdrawal symptoms in drug-dependent patients. Aim: This study sought to determine whether chronic dosing of mirtazapine during cocaine withdrawal reduced depression- and anxiety-like behaviors that characterize cocaine withdrawal in animals. Methods: Cocaine pre-treated Wistar rats were subjected to a 60-day cocaine withdrawal period during which depression- and anxiety-like behaviors were evaluated in open field tests (OFT), the elevated plus-maze (EPM), the light–dark box test (LDT), the forced swimming test (FST) and spontaneous locomotor activity (SLA). Results: We found that chronic dosing with different doses of mirtazapine (30 and 60 mg/kg) decreased depression- and anxiety-like behaviors induced by different doses of cocaine (10, 20 and 40 mg/kg) during the 60-day cocaine withdrawal. Interpretation: Our results suggest that the pharmacological effect of mirtazapine on its target sites of action (α2-adrenergic and 5-HT2A and 5-HT3 receptors) within the brain may improve depression- and anxiety-like behaviors for long periods. Conclusion: Therefore, the findings support the use of mirtazapine as a potentially effective therapy to reduce anxiety and depressive-like behavior during cocaine withdrawal.

SUMMARYDrug addiction is one of the most important health problems in the world. This psychiatry disease results in the death of about 500 000 individuals annually in the world. Despite this scenario, the development of effective drug therapies against this disease has been slow and not very successful. In recent years, new alternative pharmacological strategies against drug addiction have been designed and validated. Among them are vaccines against drugs like nicotine, morphine or cocaine and their subsequent use in immunotherapeutic pharmacological procedures for the treatment of addictive behaviors of drug consumption, both in animal models and in humans.These strategies are based on the experimental design and synthesis of various structural formulations of therapeutic vaccines against drugs of abuse. When dosed in active immunization schedules, they induce the production of specific antibodies, which recognize and bind these substances in the intravascular space and prevent the drug permeability through the blood brain barrier, resulting in decreased effects of drugs into the brain.In 2006, our research group at the National Institute of Psychiatry Ramón de la Fuente Muñiz (INPRFM) achieved and consolidated the design, synthesis, application and validation of immunoprotective therapeutic effects against relapse to morphine/heroin addiction in a rodent animal model, a model vaccine for potential human use against addiction to morphine/heroin. This model shows immunogenic capacities (high and sustained titers of highly specific antibodies) and immunoprotection (attenuates the effect up to 15mg/kg sc morphine) that the structural vaccine models competing have not been matched, which makes it the leading vaccine model against the addictive effects of heroin and morphine.Key words: Addiction, morphine/heroin, vaccines, immunotherapy, active and passive immunization. RESUMENLa adicción a una droga de abuso representa uno de los problemas sanitarios más importantes ya que esta patología genera la muerte de cerca de 500 000 sujetos anualmente en el mundo. A pesar de este panorama, el desarrollo de terapias farmacológicas efectivas contra esta enfermedad es lento y poco exitoso. En los últimos años se han diseñado y validado nuevas estrategias farmacológicas alternativas contra la adicción a drogas de abuso, como las vacunas y su uso en procedimientos farmacológicos inmunoterapéuticos para el tratamiento de esas conductas tanto en modelos de animales como en el humano.Estas nuevas estrategias experimentales están basadas en el diseño y síntesis de diversas formulaciones estructurales de vacunas terapéuticas contra las sustancias de abuso las cuales, al ser dosificadas en esquemas de inmunización activa, inducen la producción de anticuerpos séricos específicos que reconocen y se unen a estas sustancias en el espacio intravascular sistémico e impiden que crucen la barrera hematoencefálica, con lo cual disminuyen sus efectos en el cerebro.En el año 2006 nuestro grupo de trabajo en el Instituto Nacional de Psiquiatría R...

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Introduction Several studies mention that early consumption of cannabis, alcohol, or even cocaine is related to an increase in the prevalence of daily consumption of tobacco in adulthood. However, other factors, such as genetic comorbidity, social influences, and even molecular, neurochemical, and behavioral alterations induced by prenatal and postnatal cocaine exposure, could also explain these observations, since these factors together increase the vulnerability of the offspring to the reinforcing effects of nicotine. The objective of this study was to determine the effect of prenatal and postnatal exposure to cocaine on nicotine-induced locomotor sensitization in young and adult rats. Methods The study was divided into two stages: prenatal and postnatal. In the prenatal stage, a group of pregnant female Wistar rats was administered cocaine daily from day GD0 to GD21 (cocaine preexposure group), and another group of pregnant female rats was administered saline daily (saline preexposure group). Of the litters resulting from the cocaine preexposed and saline preexposed pregnant female groups, in the postnatal stage, only the male rats were used for the recording of the locomotor activity induced by different doses of nicotine (0.2, 0.4, 0.6 mg/Kg) during the induction and expression of locomotor sensitization at different postnatal ages (30, 60, 90 and 120 days). Results Prenatal and postnatal cocaine exposure enhanced nicotine-induced locomotor activity and locomotor sensitization. Conclusions This suggests that prenatal and postnatal cocaine exposure can result in increased vulnerability to other drugs of abuse, such as nicotine, in humans. Implications Several studies have shown that the abuse of a drug, such as cannabis, alcohol, or even cocaine, at an early age can progress to more severe levels of use of other drugs, such as nicotine, to adulthood. Our data are consistent with this hypothesis, since prenatal and postnatal cocaine exposure enhanced the nicotine-induced increase in locomotor activity and locomotor sensitization. This suggests that prenatal and postnatal exposure to cocaine enhances the drug's salience.