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


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.
Arce
Estibaliz
E
Department of Psychiatry, Laboratory of Biological Dynamics and Theoretical Medicine, University of California San Diego, 8950 Villa La Jolla Dr., Suite C213, La Jolla, CA 92037-0985, USA. esarce@ucsd.edu
Miller
Daniel A
DA
Feinstein
Justin S
JS
Stein
Murray B
MB
Paulus
Martin P
MP
D000284:Administration, Oral; D000293:Adolescent; D000328:Adult; D000679:Amygdala / Q000187:drug effects; D014151:Anti-Anxiety Agents / Q000008:administration & dosage / Q000494:pharmacology*; D001931:Brain Mapping; D003657:Decision Making / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005260:Female; D018755:GABA Agonists / Q000008:administration & dosage / Q000494:pharmacology*; D006801:Humans; D008032:Limbic System / Q000187:drug effects*; D008140:Lorazepam / Q000008:administration & dosage / Q000494:pharmacology*; D008279:Magnetic Resonance Imaging; D008297:Male; D017397:Prefrontal Cortex / Q000187:drug effects; D011678:Punishment; D012016:Reference Values; D012201:Reward; D012309:Risk-Taking
D014151:Anti-Anxiety Agents; D018755:GABA Agonists; D008140:Lorazepam