Acute dopamine depletion with branched chain amino acids decreases auditory top-down event-related potentials in healthy subjects

Abstract

Cerebral dopamine homeostasis has been implicated in a wide range of cognitive processes and is of great pathophysiological importance in schizophrenia. A novel approach to study cognitive effects of dopamine is to deplete its cerebral levels with branched chain amino acids (BCAAs) that acutely lower dopamine precursor amino acid availability. Here, we studied the effects of acute dopamine depletion on early and late attentive cortical processing. Auditory event-related potential (ERP) components N2 and P3 were investigated using high-density electroencephalography in 22 healthy male subjects after receiving BCAAs or placebo in a randomized, double-blind, placebo-controlled crossover design. Total free serum prolactin was also determined as a surrogate marker of cerebral dopamine depletion. Acute dopamine depletion increased free plasma prolactin and significantly reduced prefrontal ERP components N2 and P3. Subcomponent analysis of N2 revealed a significant attenuation of early attentive N2b over prefrontal scalp sites. As a proof of concept, these results strongly suggest that BCAAs are acting on basic information processing. Dopaminergic neurotransmission seems to be involved in auditory top-down processing as indexed by prefrontal N2 and P3 reductions during dopamine depletion. In healthy subjects, intact early cortical top-down processing can be acutely dysregulated by ingestion of BCAAs. We discuss the potential impact of these findings on schizophrenia research.

Figure 1

Plasma prolactin levels at baseline and up to 5 hours after administration of placebo or branched-chain amino acids (BCAA). * p< .01.

Figure 2

Grand average ERP by treatment status in response to target stimuli for selected channels in topographic head montage (right) and for midline electrodes Fz, FCz, Cz, and Pz (left).

Figure 3

Grand average ERP for midline electrode FCz. (a) Grand average ERP in response to target and standard stimuli following placebo administration. (b) Grand average ERP in response to target and standard stimuli following BCAA administration. (c) Grand average ERP difference waves (target minus standard ERP) by treatment modality.