Modulation of human risky decision making by flunitrazepam.
BACKGROUND
GABA-modulating drugs produce disinhibitory effects that increase the probability of risk-taking behavior. Previous reports suggest that the misuse of the benzodiazepine flunitrazepam is associated with several forms of harmful risky behavior, including theft, violence, and intoxication-related auto accidents.


OBJECTIVE
The present study examined the dose-response relationships between acute flunitrazepam administration and human decision making under conditions of risk. The analyses also examined flunitrazepam-mediated changes in decision-making processes using a computational modeling approach, the expectancy valence model (EVM).


METHODS
Using a laboratory measure of risky decision making designed to address acute drug effects, 12 adults were administered placebo, 0.5, 1.0, and 2.0 mg/70 kg flunitrazepam in a within-subject, repeated measures counterbalanced design. Flunitrazepam was compounded and doses were administered in an 8-oz liquid solution. Primary data analyses examined subjective effects, response rates, distribution of choices between the risky and nonrisky option, and personality correlates related to peak drug effects. Individual-subject data were submitted to a computational modeling analysis (EVM) that provided parameter estimates corresponding to components of valence; updating expectancies about alternatives (learning/memory); and consistency between choices and expected outcomes (sensitivity to learned outcomes).


RESULTS
Flunitrazepam produced dose-related changes in subjective effects and response rates, and increased selection of the risky response option. High doses significantly changed decision-making processes related to the learning/memory and consistency parameters.


CONCLUSIONS
At sufficiently high doses, flunitrazepam can engender increases in risky decision making. Globally, these changes appear similar to previous effects we have observed after acute administration of alcohol and alprazolam. As suggested by the EVM outcomes, the mechanisms underlying the changes in risky decision making are more similar to alprazolam than alcohol.
Lane
Scott D
SD
Psychiatry and Behavioral Sciences, University of Texas Health Science Center-Houston, 1300 Moursund Street, Houston, TX, 77030, USA. scott.d.lane@uth.tmc.edu
Cherek
Don R
DR
Nouvion
Sylvain O
SO
D000284:Administration, Oral; D000328:Adult; D000465:Algorithms; D000704:Analysis of Variance; D014151:Anti-Anxiety Agents / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology; D003198:Computer Simulation; D003657:Decision Making / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D005260:Female; D005445:Flunitrazepam / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology*; D006207:Half-Life; D006801:Humans; D007858:Learning / Q000187:drug effects; D008297:Male; D008568:Memory / Q000187:drug effects; D011594:Psychometrics / Q000379:methods; D012309:Risk-Taking; D012737:Sex Factors
D014151:Anti-Anxiety Agents; D005445:Flunitrazepam