Association study of 37 genes related to serotonin and dopamine neurotransmission and neurotrophic factors in cocaine dependence

Abstract

Cocaine dependence is a neuropsychiatric disorder in which both environmental and genetic factors are involved. Several processes, that include reward and neuroadaptations, mediate the transition from use to dependence. In this regard, dopamine and serotonin neurotransmission systems are clearly involved in reward and other cocaine-related effects, whereas neurotrophic factors may be responsible for neuroadaptations associated with cocaine dependence. We examined the contribution to cocaine dependence of 37 genes related to the dopaminergic and serotoninergic systems, neurotrophic factors and their receptors through a case-control association study with 319 single nucleotide polymorphisms selected according to genetic coverage criteria in 432 cocaine-dependent patients and 482 sex-matched unrelated controls. Single marker analyses provided evidence for association of the serotonin receptor HTR2A with cocaine dependence [rs6561333; nominal P-value adjusted for age = 1.9e−04, odds ratio = 1.72 (1.29-2.30)]. When patients were subdivided according to the presence or absence of psychotic symptoms, we confirmed the association between cocaine dependence and HTR2A in both subgroups of patients. Our data show additional evidence for the involvement of the serotoninergic system in the genetic susceptibility to cocaine dependence.

Attenuation of morphine withdrawal signs, blood cortisol and glucose level with forced exercise in comparison with clonidine

“…[202122] The maintenance therapy of drug addiction is based on using or manipulating specific neurotransmitters reuptake, cerebral amino acids. [2324] In this study, we have forced the animals to exercise with treadmill and combined this with clonidine, as standard treatment of dependency, and showed significant attenuation of withdrawal signs in comparison with positive control group (dependent without treatment). Also, dependent group under treatment by clonidine (0.4 mg/kg) alone showed significant decrease in signs and its severity.…”

Association of the PLCB1 gene with drug dependence

“…1 ). Population stratification was previously discarded in our sample 34 . The study was approved by the ethics committee of our institution, the Institutional Review Board of the University of Barcelona (IRB00003099), and informed consent was obtained from all participants, in accordance with the Helsinki Declaration.…”

Genetic factors in exercise adoption, adherence and obesity

“…Importantly, genes involved in dopamine and serotonin systems which are thought to be associated with exercise behaviour and adherence are also associated with addictive/compulsive behaviour. For example, SNPs within the HTR2A gene have been associated with cocaine dependence and pathological gambling , while variation in HTR1B was associated with alcohol, cocaine and heroin dependence . The A1 allele of the Taq1A polymorphism (rs1800497) within the DRD2 gene is among the most consistently replicated variants associated with alcohol dependence , while variation in DRD4 has been implicated in motivation to drink among heavy drinkers .…”