4.3 Article

Histamine H3receptor gene variants associated with drug abuse in patients with cocaine use disorder

Journal

JOURNAL OF PSYCHOPHARMACOLOGY
Volume 34, Issue 11, Pages 1326-1330

Publisher

SAGE PUBLICATIONS LTD
DOI: 10.1177/0269881120961253

Keywords

Histamine H(3)receptor; cocaine use disorder; genetic polymorphisms

Funding

  1. Ministerio de Sanidad, Servicios Sociales e Igualdad (Plan Nacional sobre Drogas), Spain [PNSD 2016I025]
  2. Instituto de Salud Carlos III (Red de Trastornos Adictivos), Spain [RD16/0017/0017]
  3. PE I+D+i 2013-2016 - ISCIII [PT17/0019]
  4. ERDF

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Background: Preclinical work revealed significant interactions between ligands of the histamine H(3)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 H(3)receptor (pitolisant) has reached the market after approval for the treatment of narcolepsy. Aims: We have studied associations between histamine H(3)receptor gene variants and cocaine use disorder to increase the knowledge of the possible involvement of histamine H(3)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 H(3)receptor function could be relevant in drug abuse in general and cocaine addiction in particular.

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