Cocaine(p) [HRP]

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.

Objective. To explore the optimal time points for deep brain stimulation (DBS) on the treatment of morphine addiction and its possible mechanisms by investigating how high-frequency stimulation (HFS) in bilateral nucleus accumbens (NAc) at different time points influences the addictive behaviors of rats with drug addiction. Methods. The rats were randomly divided into extinction stimulation group (n = 20) and postextinction stimulation group (n = 20). Ten rats in the extinction stimulation group were treated using 120 Hz HFS during extinction stage while another 10 rats with pseudostimulation were served as control group. The CPP scores were evaluated at the second day after intervention, with total 9 sections accomplished. The CPP scores were evaluated at the second day of the intervention. In the postextinction stimulation group, 120 Hz HFS was intervened during the postextinction stage in 10 experimental rats and pseudostimulation was performed in 10 control rats. Stimulation was performed for 7 days continuously, and a small dose of morphine was administrated to induce relapse after the postextinction period. Results. During the extinction phase, CPP scores after HFS were significantly higher. During the postextinction phase, relapse CPP scores after HFS were dramatically lower. Conclusion. HFS of bilateral NAc inhibits the extinction of addictive behavior during the extinction phase, and HFS during the postextinction period suppresses relapse of drug seeking behavior.