Original Investigation

Psychopharmacology

, Volume 189, Issue 1, pp 105-116

Lorazepam dose-dependently decreases risk-taking related activation in limbic areas

  • Estibaliz ArceAffiliated withDepartment of Psychiatry, Laboratory of Biological Dynamics and Theoretical Medicine, University of California San Diego Email author 
  • , Daniel A. MillerAffiliated withDepartment of Psychiatry, Laboratory of Biological Dynamics and Theoretical Medicine, University of California San Diego
  • , Justin S. FeinsteinAffiliated withDepartment of Psychiatry, Laboratory of Biological Dynamics and Theoretical Medicine, University of California San Diego
  • , Murray B. SteinAffiliated withDepartment of Psychiatry, Laboratory of Biological Dynamics and Theoretical Medicine, University of California San DiegoPsychiatry Service, San Diego Veterans Affairs Medical Center
  • , Martin P. PaulusAffiliated withDepartment of Psychiatry, Laboratory of Biological Dynamics and Theoretical Medicine, University of California San DiegoPsychiatry Service, San Diego Veterans Affairs Medical Center

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Abstract

Rationale

Several studies have examined the role of different neurotransmitter systems in modulating risk-taking behavior.

Objective

This investigation was aimed to determine whether the benzodiazepine lorazepam dose-dependently alters risk-taking behavior and underlying neural substrates.

Materials and methods

Fifteen healthy, nonsmoking, individuals (six women, nine men), aged 18–39 years (mean 27.6 ± 1.4 years) with 12–18 years of education (mean 15.6 ± 0.3 years) underwent functional magnetic resonance imaging while performing a risk-taking decision-making task.

Results

Our results show that lorazepam did not affect risky behavior at 0.25 and 1 mg, but dose-dependently attenuated activation in (a) the amygdala and medial prefrontal cortex during the response selection phase, and in (b) the bilateral insular cortex and amygdala during the outcome (i.e., rewarded or punished) phase. Furthermore, a lorazepam-induced increase in insular cortex activation was associated with less risky responses.

Conclusions

Taken together, our findings support the idea that GABAergic modulation in limbic and paralimbic structures is important during both the response selection and outcome phase of risk-taking decision-making.

Keywords

Risk-taking Decision-making fMRI Insula Amygdala Medial prefrontal cortex GABAergic Lorazepam