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

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.

Figure 1

Punished and non-punished risky responses for 0mg, 0.25mg, and 1mg of lorazepam.

Figure 2

Lorazepam effect regions of interest analysis: Areas of significant BOLD activation in limbic areas during Risky versus Safe responses.

Figure 3

Correlation scatter plot between lorazepam's effect on insula activation during Risky versus Safe responses and percentage of risky responses.

Figure 4

Lorazepam effect whole brain analysis: Areas of significant BOLD activation during Punished vs non-Punished.

Figure 5

Lorazepam effect regions of interest analysis: Areas of significant BOLD activation in limbic areas during Punished vs non-Punished.