Zolmitriptan and human aggression: interaction with alcohol

Abstract

Rationale: The serotonin 1(B/D) (5-HT1(B/D)) receptor has shown potential as a target for decreasing aggression. The 5-HT1(B/D) agonist zolmitriptan's ability to reduce aggressive behavior in humans and its interaction with the well-known aggression-enhancing drug alcohol were examined.

Objectives: Our objective was to investigate zolmitriptan's potential to modify human aggression in a laboratory paradigm across a range of alcohol doses. Alcohol has been consistently associated with aggression and violence, thus we hoped to expand current understanding of alcohol's role in aggressive behavior via manipulation of the serotonin (5-HT) system.

Methods: Eleven social drinkers, seven male, were recruited to participate in a research study lasting 3-4 weeks. Aggression was measured using the point-subtraction aggression paradigm (PSAP), a laboratory model widely used in human aggression studies. Subjects were administered 5-mg zolmitriptan and placebo capsules along with alcohol doses of 0.0, 0.4 and 0.8 g/kg in a within-subject, counterbalanced dosing design. Data were analyzed as the ratio of aggressive/monetary-earning responses, to account for possible changes in overall motor function due to alcohol.

Results: There was a significant alcohol by zolmitriptan interaction on the aggressive/monetary response ratio. Specifically, compared to placebo, zolmitriptan decreased the aggressive/monetary ratio at the 0.4- and 0.8-g/kg alcohol doses.

Conclusions: A 5-mg dose of zolmitriptan effectively reduced alcohol-related aggression in an acute dosing protocol, demonstrating an interaction of 5-HT and alcohol in human aggressive behavior.

Fig. 1

Ratio of number of aggressive/monetary responses (Y axis) across each of the five daily test sessions and each of the alcohol dosing conditions (X axis). Each data point shows the mean (±SEM) for the 11 subjects. Black circles show 0-mg zolmitriptan (placebo) and open circles show 5-mg zolmitriptan doses

Fig. 2

Summary of the ratio of number of aggressive/monetary responses (Y axis) averaged over five daily test sessions (mean of Fig. 1) across each of the alcohol dosing conditions (X axis). Each data point shows the mean (±SEM) for the 11 subjects. Black circles show 0-mg zolmitriptan (placebo) and open circles show 5-mg zolmitriptan doses. The figure summarizes graphically the significant alcohol × Zomig interaction revealed in repeated-measures ANOVA. See text for details