Effects of Acute Tryptophan Depletion Moja-De on Behavioral Inhibition in Healthy Adults

Abstract

Video presentation of the entire lecture can be accessed here . Background : Alterations in serotonergic (5-HT) neurotransmission are thought to play a decisive role in affective disorders and impulse control. However, the studies on the involvement of cerebral 5-HT availability and its effects on behavioral inhibition in healthy subjects yielded inconsistent findings. It appears that central nervous serotonergic neurotransmission is rather related to context-specific aspects of suppression of behavior than motor response inhibition alone. Crockett et al. aimed to disentangle the involvement of 5-HT on aspects of motor response inhibition, punishment-induced suppression of inappropriate responses, and sensitivity toward aversive outcomes in a single behavioral Go-NoGo task using a fixed dosage acute tryptophan depletion (ATD) procedure. While motor response inhibition was unaffected, punishmentinduced inhibition was reported to be abolished by ATD. Objective : A recently developed refined and body-weight-adjusted ATD protocol (Moja-De) was applied. We aimed to replicate the experiment of Crockett et al. using a Go-NoGo task in a comparable sample of young healthy adults. Methods : Central nervous 5-HT synthesis was lowered by administering a body-weight-adapted ATD procedure in a randomized, double-blind, within-subject, repeated measures design in 24 healthy volunteers. A tryptophan-balanced amino acid beverage served as a control condition. The above-mentioned Go-NoGo task was administered 180 minutes after beverage intake. Blood samples were obtained at four time points: baseline, 90 minutes, 180 minutes, and 270 minutes after beverage administration. Results : ATD produced significant depletion of plasma levels of both total and free tryptophan at all post- ATD time points, compared with a balanced amino acid load (BAL). While overall Go-NoGo performance accuracy was not affected by ATD, response times significantly decreased. Also, the ability to adjust behavioral responding in regard to aversive outcome magnitude and behavioral adjustments following error contingent punishment remain intact after decreased brain 5-HT synthesis. However, no dissociation effect of ATD on punishment-induced inhibition was observed. Conclusion : Our study using a recently developed refined and individually adjusted tryptophan depletion procedure assessed with the identical behavioral task as used by Crockett et al. yielded challenging results compared with the original study in terms of the role of 5-HT in behavioral inhibition. Our findings suggest that ATD Moja-De facilitates adequate responding (improved response times) at equally low performance accuracy, compared with BAL. ATD-specific reductions in punishment-induced inhibition were not observed in the present sample, thus challenging the suggested role of 5-HT related to the aversive context of inhibitory behavior in the original study. Overall, our results suggest that body weight adjusted Moja-De trypthophan depletion does not result in disruptions of punishment related behavioral functioning. The use of a more refined and individually adjusted depletion procedure might, at least in part, explain the discrepancies between the two studies. (Published: 9 September 2013) Citation: Translational Developmental Psychiatry 2013, 1 : 18676 - http://dx.doi.org/10.3402/tdp.v1i0.18676