Plasma midkine levels in patients with cocaine use disorder during abstinence. / Plasma midkine levels in patients with cocaine use disorder during abstinence.

Preclinical evidence suggests that endogenous midkine could play a key modulatory role on the neurotoxic and addictive effects of different kinds of drugs of abuse, including psychostimulants. However, this hypothesis has not yet been explored in humans. As a first approach to progress in this knowledge, we have comparatively studied plasma midkine levels in 75 patients with cocaine use disorder under abstinence and 26 control subjects matched for sex, age and body mass index. Patients were further segmented into early-abstinent (up to one month of abstinence, n = 30) and late-abstinent (more than one month of abstinence, n = 45). Midkine levels were quantified in plasma samples of all the participants by enzyme-linked immunosorbent assays. Early-abstinent patients exhibited a 60% increase of midkine plasma concentration in comparison with the controls. This elevation tended to normalize upon the progression of abstinence. The results obtained demonstrate that peripheral midkine levels are closely related to cocaine use and are consistent with the idea that this cytokine could play a protective role by limiting the biological activity of psychostimulants.

Diversos estudios preclínicos han sugerido que la midkina endógena podría jugar un papel modulador clave sobre los efectos neurotóxicos y adictivos de distintas drogas, incluidos los psicoestimulantes. Esta hipótesis no ha sido aún explorada en humanos. Como primer paso en esta dirección, en el presente trabajo hemos medido los niveles plasmáticos de midkina en 75 pacientes con trastorno por uso de cocaína en abstinencia y 26 controles apareados con los anteriores por sexo, edad e índice de masa corporal. Los pacientes fueron además divididos en un grupo de abstinencia temprana (menos de un mes, n = 30) y otro de abstinencia tardía (más de un mes, n = 45). Se cuantificaron los niveles plasmáticos de midkina de todos los participantes mediante un ensayo por inmunoabsorción ligado a enzimas. Los pacientes en abstinencia temprana mostraron un incremento del 60% en su concentración plasmática de midkina con respecto a los controles que tendió a desaparecer en los pacientes con periodos de abstinencia más prolongados. Los resultados demuestran que los niveles periféricos de midkina están estrechamente relacionados con el uso de cocaína y apoyan la idea de que dicha citoquina podría jugar un papel protector limitando la actividad biológica de los psicoestimulantes.

Histamine H3 receptor gene variants associated with drug abuse in patients with cocaine use disorder.

BACKGROUND: Preclinical work revealed significant interactions between ligands of the histamine H3 receptor and different drugs of abuse. In the case of psychostimulants, the results reported are somewhat controversial and human data are still scarce, despite the fact that an inverse agonist of the H3 receptor (pitolisant) has reached the market after approval for the treatment of narcolepsy. AIMS: We have studied associations between histamine H3 receptor gene variants and cocaine use disorder to increase the knowledge of the possible involvement of histamine H3 receptor in drug abuse. METHODS: Seven single nucleotide polymorphisms of the histamine H3 receptor gene were genotyped by using a multiplexing assay in 248 samples of subjects with cocaine use disorder and 500 randomized samples of subjects representative of the Spanish population. RESULTS: The study of the epidemiological information associated to the samples revealed that subjects with cocaine use disorder broadly abused alcohol, tobacco and cannabinoids. Two single nucleotide polymorphisms (rs3787430 and rs74627870) were found significantly associated with the occurrence of addiction and one more (rs13042865) was specifically related to the severity of cocaine dependence within drug abusers. CONCLUSIONS: The associations found in this study further extend the hypothesis that histamine H3 receptor function could be relevant in drug abuse in general and cocaine addiction in particular.