Prefrontal Cortex Activation and Stopping Performance Underlie the Beneficial Effects of Atomoxetine on Response Inhibition in Healthy Volunteers and Those With Cocaine Use Disorder.
Biol Psychiatry Cogn Neurosci Neuroimaging
; 7(11): 1116-1126, 2022 11.
Article
em En
| MEDLINE
| ID: mdl-34508901
ABSTRACT
BACKGROUND:
Impaired response inhibition in individuals with cocaine use disorder (CUD) is hypothesized to depend on deficient noradrenergic signaling in corticostriatal networks. Remediation of noradrenergic neurotransmission with selective norepinephrine reuptake inhibitors such as atomoxetine may therefore have clinical utility to improve response inhibitory control in CUD.METHODS:
We carried out a randomized, double-blind, placebo-controlled, crossover study with 26 participants with CUD and 28 control volunteers investigating the neural substrates of stop-signal inhibitory control. The effects of a single dose of atomoxetine (40 mg) were compared with placebo on stop-signal reaction time performance and functional network connectivity using dynamic causal modeling.RESULTS:
We found that atomoxetine speeded Go response times in both control participants and those with CUD. Improvements in stopping efficiency on atomoxetine were conditional on baseline (placebo) stopping performance and were directly associated with increased inferior frontal gyrus activation. Further, stopping performance, task-based brain activation, and effective connectivity were similar in the 2 groups. Dynamic causal modeling of effective connectivity of multiple prefrontal and basal ganglia regions replicated and extended previous models of network function underlying inhibitory control to CUD and control volunteers and showed subtle effects of atomoxetine on prefrontal-basal ganglia interactions.CONCLUSIONS:
These findings demonstrate that atomoxetine improves response inhibition in a baseline-dependent manner in control participants and in those with CUD. Our results emphasize inferior frontal cortex function as a future treatment target owing to its key role in improving response inhibition in CUD.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Cocaína
/
Inibidores da Captação Adrenérgica
Tipo de estudo:
Clinical_trials
/
Prognostic_studies
Limite:
Humans
Idioma:
En
Revista:
Biol Psychiatry Cogn Neurosci Neuroimaging
Ano de publicação:
2022
Tipo de documento:
Article