Cannabis and cocaine decrease cognitive impulse control and functional corticostriatal connectivity in drug users with low activity DBH genotypes.
The dopamine β-hydroxylase (DβH) enzyme transforms dopamine into noradrenaline. We hypothesized that individuals with low activity DBH genotypes (rs1611115 CT/TT) are more sensitive to the influence of cannabis and cocaine on cognitive impulse control and functional connectivity in the limbic 'rewar...
| Publicado en: | Brain Imaging & Behavior Vol. 10; no. 4; pp. 1254 - 1264 |
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| Autores principales: | , , , , , , , , , , , , , , , |
| Formato: | research randomized controlled trial Journal Article |
| Publicado: |
Springer Nature
Dec2016
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| Acceso en línea: | Ver este registro en EBSCOhost |
| fields | @attributes: recordID: 1 pdfLink: plink: https://search.ebscohost.com/login.aspx?direct=true&db=ccm&AN=120010868&site=ehost-live header: @attributes: shortDbName: ccm uiTerm: 120010868 longDbName: CINAHL Complete uiTag: AN controlInfo: bkinfo: dissinfo: jinfo: jid: 19317557 3GSC jtl: Brain Imaging & Behavior issn: 19317557 maglogo: N pubinfo: dt: Dec2016 vid: 10 iid: 4 pid: 237 pub: Springer Nature place: New York, New York artinfo: ui: 120010868 120010868 NLM26667034 120010868 10.1007/s11682-015-9488-z NLM26667034 120010868 ppf: 1254 ppct: 10 formats: fmt: @attributes: type: P tig: atl: Cannabis and cocaine decrease cognitive impulse control and functional corticostriatal connectivity in drug users with low activity DBH genotypes. aug: au: Ramaekers, J. Wel, J. Spronk, D. Franke, B. Kenis, G. Toennes, S. Kuypers, K. Theunissen, E. Stiers, P. Verkes, R. Ramaekers, J G van Wel, J H Toennes, S W Kuypers, K P C Theunissen, E L Verkes, R J affil: Department of Neuropsychology and Psychopharmacology, Faculty of Psychology and Neuroscience , Maastricht University , Maastricht The Netherlands sug: subj: Behavior Cocaine Adverse Effects Brain Drug Effects Psychotropic Drugs Adverse Effects Oxidoreductases Cannabis Adverse Effects Cannabis Pharmacokinetics Neural Pathways Neuropsychological Tests Crossover Design Male Substance Use Disorders Substance Use Disorders Psychosocial Factors Cocaine Pharmacokinetics Cocaine Blood Cannabis Brain Physiopathology Female Relaxation Psychotropic Drugs Administration and Dosage Cognition Brain Cannabis Administration and Dosage Executive Function Human Brain Mapping Executive Function Drug Effects Substance Use Disorders Physiopathology Psychotropic Drugs Blood Young Adult Psychotropic Drugs Pharmacokinetics Magnetic Resonance Imaging Neural Pathways Drug Effects Double-Blind Studies Cocaine Administration and Dosage Neural Pathways Physiopathology Cognition Drug Effects Validation Studies Comparative Studies Evaluation Research Multicenter Studies Randomized Controlled Trials Male Female ab: The dopamine β-hydroxylase (DβH) enzyme transforms dopamine into noradrenaline. We hypothesized that individuals with low activity DBH genotypes (rs1611115 CT/TT) are more sensitive to the influence of cannabis and cocaine on cognitive impulse control and functional connectivity in the limbic 'reward' circuit because they experience a drug induced hyperdopaminergic state compared to individuals with high activity DBH genotypes (rs1611115 CC). Regular drug users (N = 122) received acute doses of cannabis (450 μg/kg THC), cocaine HCl 300 mg and placebo. Cognitive impulse control was assessed by means of the Matching Familiar Figures Test (MFFT). Resting state fMRI was measured in a subset of participants to determine functional connectivity between the nucleus accumbens (NAc) and (sub)cortical areas. The influence of cannabis and cocaine on impulsivity and functional connectivity significantly interacted with DBH genotype. Both drugs increased cognitive impulsivity in participants with CT/TT genotypes but not in CC participants. Both drugs also reduced functional connectivity between the NAc and the limbic lobe, prefrontal cortex, striatum and thalamus and primarily in individuals with CT/TT genotypes. Correlational analysis indicated a significant negative association between cognitive impulsivity and functional connectivity in subcortical areas of the brain. It is concluded that interference of cannabis and cocaine with cognitive impulse control and functional corticostriatal connectivity depends on DBH genotype. The present data provide a neural substrate and behavioral mechanism by which drug users can progress to drug seeking and may also offer a rationale for targeted pharmacotherapy in chronic drug users with high risk DBH genotypes. pubtype: Academic Journal doctype: research randomized controlled trial Journal Article ougenre: Article language: English refInfo: holdings: @attributes: islocal: N |
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